Stem Cells - a global review, and how to boost your body's regeneration machine

Stem Cells – what are, and how, where, when, and should we use, stem cells to regenerate and renew parts of our body?

March 7th, 2022 <40 minute read.

Can we harness the bodies own repair and maintenance mechanisms, ie stem cells, to substantially extend a humans healthspan or repair various health problems in the body? The answer is, at present, in 2022, “possibly”, depending on the situation, and in the future “probably”, with great potential on the horizon.

The human body comprises more than 220 types of cells, and every one of these cell types arises from the zygote, the single cell that forms when an egg is fertilized by a sperm. Within a few days of fertilisation, that single cell divides over and over again until it forms a blastocyst, a hollow ball of 150 to 200 cells that give rise to every single cell type a human body needs to survive and thrive, including the umbilical cord and the placenta that nourishes the developing fetus.

As you were made by stem cells, you are then “maintained and repaired” by stem cells, some from stem cells left in the tissue, or from “factories” in the bone marrow. But as we age, our reservoirs of functional stem cells become depleted; some stem cells die, some become corrupted, and some simply go to sleep for decades ie become dormant. Stem cells and their secretomes (other factors secreted by the stem cells that can affect surrounding and distant cells) are one of the bodies most important maintenance and regeneration, and even growth, tools to keep a human vibrant and in “good working order.”

The question then becomes is are there ways to extend or improve the repair and maintenance function of stem cells, which I address in this note.

Sometimes called the body’s “master cells,” stem cells, as mentioned, are the cells that develop into blood, brain, bones, and all of the body’s organs. They have the potential to repair, restore, replace, and regenerate cells, in tissues and organs, and boost or maintain the immune system, and can currently be used to treat some medical conditions and diseases, with many more to follow over coming years.

Stem cells are defined by two properties.

First, they can ‘self-renew,’ that is they can divide and give rise to more stem cells of the same kind.

Second, they can mature or ‘differentiate’ into specialized cells that carry out a specific function, such as in the skin, muscle, or blood.

There are a number of different types of stem cells. These include embryonic stem cells that exist only at the earliest stages of development; and various types of ‘tissue-specific’ stem cells (sometimes referred to as ‘adult’ or ‘somatic’ stem cells) that are found in various tissues in our bodies.

Recently, cells with properties similar to embryonic stem cells, referred to as induced pluripotent stem cells (iPS cells), have been engineered from specialized cells such as skin or fat cells. Factors are applied to these adult stem cells to make them younger and turn in to “blank slate” stem cells, which are then reprogrammed to become a range of cells eg brain cells -neurons, skeleton cells etc. If you want to order some” see bit.bio | synthetic biology | precision engineered human cells . (Do not call them “brains in a dish..”!)

The author has invested in several stem cell secretome companies that are targeting regeneration of parts of the human body, and the immune system, where one is in human clinical trials.

So I also look at the state of the art in using stem cells to address a malady at any age, and where we are at and hope to be to rejuvenate underperforming organs or tissues.

There are stem cells circulating in your body every day, but if there is damage then more are produced and they rush to fix anything broken. However as you older they become less effective, they replicate more slowly so repair wounds more slowly or not at all. Some scientists believe that you have a limited “bank” of stem cells, so if you make a withdrawal from your stem cell bank -say for a major injury- so will have less stem cells for injuries when you get older. To my knowledge, this belief has not been scientifically validated.

I also touch on cyrobanking some of your stem cells (“SCB” = Stem Cell Banking) where people do this in the hope of the unfreezing them when then need them when you are older ie having a “younger and better” generation of your own stem cells, then this may or may not help better repair any injury you may get when you are older. Seems to make sense- have more effective stem cells for that older injury… but currently science is not at a point where you can reliably unfreeze and then use them.

And for the avoidance of doubt, this is not medical advice and anyone seeking treatment for something needs to consult with their licenced medical professional.

This note is divided in to the following sections:

1) What are stem cells, what do they do and how do they work?

2) Where do they come from and where do they go?

3) How can stem cells be manipulated ie adapted to help us repair better?

4) Cautions about using stem cells, and what to know beforehand

5) What and where are stem cell therapies in use today eg clinics etc; what are the potential benefits; and risks, and should one cyrobank some stem cells?

6) What advances can we expect by when?

7) Summary

1) What are stem cells, what do they do and how do they work?

You were created from stem cells.

A sperm fuses with an oocyte (the female egg) and creates a single cell, called a Zygote, and at the moment of fertilisation , there is a flash of light and new life begins. This Zygote is the ultimate stem cell, referred to as the totipotent stem cell, due to its high degree of plasticity.

The zygote, becomes the blastocyst, or embryonic stem cells, when the fertilised egg has only divided into 4 or 8 cells and the cells retain some totipotency – the ability to produce all cell types, splitting in two, each carrying the combined DNA of both parents, and those split in two again and so on. Hence the rapid growth, 1, 2, 4, 8, 16, 32, 64 cells, each one dividing more and more, and so on. Each of these stem cells can become anything in the human body, a brain cell, liver cell, skin cell, heart cell etc. The genome (3.2 billion base pairs) provides the instructions to the stem cells as to what they will become. At some point most of the stem cells become Mesenchymal stem cells, better known as adult stem cells, which are stem cells that can only become one type of cell in the body, eg a muscle stem cell.

The adult organism derives from a series of regulated processes involving the proliferation, migration, differentiation and maturation of different cell types.

So when a muscle cell is damaged, the muscle stem cell gets message to make another muscle cell and divides to make the new muscle cell. But as one ages these stem cells get exhausted and damaged and do not work as well, so your maintenance and repair facility begins to fail, and your body starts to have more and more problems, until you eventually die…

Or in a chart:

Source: Stem Cells, Bagnara et all

Or represented a different way:

Stem cells are responsible for tissue repair, organ maintenance, and immune system function. They have the potential to repair, restore, replace, and regenerate cells.

So fully understanding stem cells and how they work and then working out how to manipulate them and rejuvenate them can add decades of healthspan to an individual.

Different types of stem cells…

There are 3 major categories of stem cells,

· Totipotent stem cells – Have the capacity to form an entire organism.

· Pluripotent stem cells – Can give rise to most, but not all, tissues within an organism (iPSCS- induced pluripotent stem cells are other mature cells reversed to become iPSCs)

· Multipotent stem cells – Undifferentiated cells that are limited to giving rise to specific populations of cells

Embryonic stem cells. These stem cells come from embryos that are three to five days old. At this stage, an embryo is called a blastocyst and has about 150 cells.

These are pluripotent stem cells, meaning they can divide into more stem cells or can become any type of cell in the body. This versatility allows embryonic stem cells to be used to regenerate or repair diseased tissue and organs.

· Adult stem cells. These stem cells are found in small numbers in most adult tissues, such as bone marrow or fat. Compared with embryonic stem cells, adult stem cells have a more limited ability to give rise to various cells of the body.

Until recently, researchers thought adult stem cells could create only similar types of cells. For instance, researchers thought that stem cells residing in the bone marrow could give rise only to blood cells.

However, emerging evidence suggests that adult stem cells may be able to create various types of cells. For instance, bone marrow stem cells may be able to create bone or heart muscle cells.

This research has led to early-stage clinical trials to test usefulness and safety in people. For example, adult stem cells are currently being tested in people with neurological or heart disease.

Adult stem cells also are more likely to contain abnormalities due to environmental hazards, such as toxins, or from errors acquired by the cells during replication.

· Adult cells altered to have properties of embryonic stem cells (induced pluripotent stem cells). Scientists have successfully transformed regular adult cells into stem cells using genetic reprogramming. By altering the genes in the adult cells, researchers can reprogram the cells to act similarly to embryonic stem cells.

This new technique may allow researchers to use reprogrammed cells instead of embryonic stem cells and prevent immune system rejection of the new stem cells. However, scientists don't yet know whether using altered adult cells will cause adverse effects in humans.

Researchers have been able to take regular connective tissue cells and reprogram them to become functional heart cells. In studies, animals with heart failure that were injected with new heart cells experienced improved heart function and survival time.

· Perinatal stem cells. Researchers have discovered stem cells in amniotic fluid as well as umbilical cord blood. These stem cells also have the ability to change into specialized cells. Amniotic fluid fills the sac that surrounds and protects a developing fetus in the uterus. Researchers have identified stem cells in samples of amniotic fluid drawn from pregnant women to test for abnormalities — a procedure called amniocentesis.

Embryonic stem cells

Embryonic stem cells are obtained from the inner cell mass of the blastocyst, a mainly hollow ball of cells that, in the human, forms three to five days after an egg cell is fertilized by a sperm. A human blastocyst is about the size of the dot above this “i.”

In normal development, the cells inside the inner cell mass will give rise to the more specialized cells that give rise to the entire body—all of our tissues and organs. However, when scientists extract the inner cell mass and grow these cells in special laboratory conditions, they retain the properties of embryonic stem cells.

Embryonic stem cells are pluripotent, meaning they can give rise to every cell type in the fully formed body, but not the placenta and umbilical cord. These cells are incredibly valuable because they provide a renewable resource for studying normal development and disease, and for testing drugs and other therapies. Human embryonic stem cells have been derived primarily from blastocysts created by in vitro fertilization (IVF) for assisted reproduction that were no longer needed.

Tissue-specific stem cells

Tissue-specific stem cells (also referred to as somatic or adult stem cells) are more specialized than embryonic stem cells. Typically, these stem cells can generate different cell types for the specific tissue or organ in which they live.

For example, blood-forming (or hematopoietic) stem cells in the bone marrow can give rise to red blood cells, white blood cells and platelets. However, blood-forming stem cells don’t generate liver or lung or brain cells, and stem cells in other tissues and organs don’t generate red or white blood cells or platelets.

Some tissues and organs within your body contain small caches of tissue-specific stem cells whose job it is to replace cells from that tissue that are lost in normal day-to-day living or in injury, such as those in your skin, blood, and the lining of your gut.

Tissue-specific stem cells can be difficult to find in the human body, and they don’t seem to self-renew in culture as easily as embryonic stem cells do. However, study of these cells has increased our general knowledge about normal development, what changes in aging, and what happens with injury and disease.ESENC STEM CELLS:

Induced pluripotent stem cells

Induced pluripotent stem (iPS) cells are cells that have been engineered in the lab by converting tissue-specific cells, such as skin or fat cells, into cells that behave like embryonic stem cells. IPS cells are critical tools to help scientists learn more about normal development and disease onset and progression, and they are also useful for developing and testing new drugs and therapies.

While iPS cells share many of the same characteristics of embryonic stem cells, including the ability to give rise to all the cell types in the body, they aren’t exactly the same. Scientists are exploring what these differences are and what they mean. For one thing, the first iPS cells were produced by using viruses to insert extra copies of genes into tissue-specific cells. Researchers are experimenting with many alternative ways to create iPS cells so that they can ultimately be used as a source of cells or tissues for medical treatments.

The following chart highlights a range of things that can cause a stem cell to malfunction and a list of diseases that can happen due to malfunctions.

Source: Ahmed ASI et al. Stem cells and aging. A proposed mechanism for the aging-induced deterioration of stem cell functions and aging-associated diseases. ROS: Reactive oxygen species

Scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory pieced together a mechanism that causes a type of human adult stem cell to permanently stop dividing after being exposed to ionizing radiation.

Aging may also shift gene functions, as reported for some genes such as, p53 and mammalian target of rapamycin (mTOR), which are beneficial in early life, but becomes detrimental later in life.

In 2021, over 64,000+ scientific publications highlight research and therapeutic advances with mesenchymal stem cells (MSCs), and over 1,400+ clinical trials are investigating therapeutic uses of MSCs. Additionally, 300,000+ scientific publications about stem cells have been released.

When placed in a petri dish with the proper nutrients, one cord stem cell will multiply into 1 billion cells in 30 days, whereas one adult stem cell will multiply into only around 200 cells in 30 days, according to a 2011 study published in the journal Orthopedics.

Red bone marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow bone marrow is made mostly of fat and contains stem cells that can become cartilage, fat, or bone cells. Bone marrow cells (BMC) are progenitors of bone, cartilage, skeletal tissue, the hematopoiesis-supporting stroma and adipocyte cells. BMCs have the potential to differentiate into neural cells, cardiac myocytes, liver hepatocytes, chondrocytes, renal, corneal, blood, and myogenic cells.

Muscle Stem Cells (MuSCs):

MuSCs are tissue resident stem cells needed for the repair and growth of muscle fibres, that are otherwise maintained in a reversible cell-cycle- arrested state called quiescence. Increasing evidence is that quiescence is dynamically regulated and contributes to stemness, the long term capacity to maintain regenerative functions. They can be classified in subpopulations with different dynamics of activation and regenerative potential.

For deeper analysis see the paper on Muscle Stem Cell quiescence, by Ancel, Trends in cell biology July 2021.

In a healthy state, these MuSCs mostly lay quiet and rarely divide but upon injury, they bolt into action by dividing and specializing into new muscle cells to help repair damaged muscle tissue. Once that mission is accomplished, the small pool of muscle stem cells is replenished through self-renewal before going back into a dormant, or quiescent, state.

The effect of aging on stem cells: Stem Cell Exhaustion

One of the 9 Hallmarks of Aging (2013 paper) is stem cell exhaustion.

The ability of our tissues and organs to regenerate and repair damage is critical to maintaining health. Our bodies’ ability to regenerate tissues and organs depends on healthy stem cells--the ultimate source of new cells--in virtually every tissue. Healthy stem cells must replicate when required, but not otherwise. The replication ability of stem cells--and their ability to replicate only when needed--declines with age. This may encompass their quality declining due to factors such as toxins or radiation damaging them; reduction in the total number of stem cells, or other factors. Several labs have now shown that stem cell function can be resuscitated by external factors such as the as-yet-unidentified rejuvenating factor(s) found in the blood of young mice or humans, opening the door for possible pharmacological prolongation of stem cell health.

Stem cells are considered to be immortal in culture and, therefore, of great interest for aging research. This immortality is regulated by increased proteostasis, which controls the quality of proteins. (Isabel Saez,. Insights into the ubiquitin-proteasome system of human embryonic stem cells. Scientific Reports, 2018). Note that a hallmark of aging is loss of proteostasis.

Scientists estimate that everyone starts their life with about 20,000 stem cells, 1,300 of which are considered “active.” To the researchers’ surprise, Hendrikje van Andel-Schipper at 115 years old, only had two active stem cells at the time of her death. They discovered that although she was a mostly healthy person, there were hundreds of genetic mutations in her cells. In Dr. Henne Holstege Lab at the VU University Medical Center in Amsterdam latest study, (in 2014) published in the journal Genome Research, the researchers looked for gene mutations in Andel-Schipper’s blood.

It has been estimated that the adult human blood compartment is populated by the offspring of approximately 10,000– 20,000 hematopoietic stem cells (HSCs) (Abkowitz et al. 2002). Human HSCs self-renew / replicate on average once every 40 weeks (range, 25-50 weeks) to create two daughter cells equivalent to their parent, and they differentiate to create offspring clones with multipotent progenitor cells that generate the much larger number of diverse blood cells via hematopoiesis (Catlin et al. 2011). These human HSCs reproduce slower than nonhuman primate HSCs (once per 25 weeks) and much slower than cats (once per 8.3 weeks) or mice (once per 2.5 weeks).

Hematopoiesis is a complex system. To ensure that blood cell production is robust (Over 10 to the power of 11 red cells, granulocytes, and platelets produced each day) and durable (maintained throughout a lifetime), the parent cells, human hematopoietic stem cells (HSCs), are tightly regulated. Emerging data suggest that this is not accomplished by a uniform population of HSCs or by prescribed (robotic) decision-making. Rather, there are significant genetic and epigenetic differences among HSCs that drive fate decisions.

2) Where do they come from and where do they go?

From conception, stem cells divide and multiply to produce the whole body. When the body is built, some adult stem cells (MSCs) are left in place in various organs and tissues, and called on when needed. Others are produced from the bone marrow and shipped out to organs and tissues that need them.

The adult stem cell population are based in the bone marrow or in the tissues themselves, which appear to be able to differentiate in fibroblasts (a type of cell found in connective tissue. Fibroblasts secrete collagen proteins that are used to maintain a structural framework for many tissues. They also play an important role in healing wounds); osteoblasts (specialized mesenchymal cells that synthesize bone matrix and coordinate the mineralization of the skeleton. These cells work in harmony with osteoclasts, which resorb bone, in a continuous cycle that occurs throughout life ) , chondroblasts (AKA perichondrial cells) are cells that play an important role in the formation of cartilage (AKA chondrogenesis). They are located in the perichondrium, which is a layer of connective tissue that surrounds developing bone and also helps protect cartilage , adipocytes (cells specialised in storing energy as fat, mainly triglycerides, in organelles called lipid droplets) and other cell types.

A stem cell line is a group of cells that all descend from a single original stem cell and are grown in a lab. Cells in a stem cell line keep growing but don't differentiate into specialized cells. Ideally, they remain free of acquired genetic defects and continue to create more stem cells. Clusters of cells can be taken from a stem cell line and frozen for storage or shared with other researchers. A stem cell line can be cultured in vitro indefinitely.

In bone marrow, MSCs constituted just 0.0001%-0.01% of all bone marrow nucleated cells. Fat tissue typically contains 100,000 MSCs in each gram of fat, and they are less affected by one’s age compared to other sources.

3) How can stem cells be manipulated ie adapted to make them repair us better?

In the USA, the FDA prohibits more than minimal manipulation of stem cells, which essentially means your own stem cells can be extracted from your body and reinjected the same day.

For years, American and other nations "stem-cell tourists" have flocked to unregulated clinics in Mexico, the Caribbean and China in search of everything from heart treatments to facelifts, seeking solutions that they cannot legally get in the USA.

In March 2021, 1,480 U.S. businesses operating 2,754 clinics were found selling purported stem cell treatments for various indications. So nearly 1,500 U.S. businesses now advertise purported stem cell therapies for a wide range of diseases and injuries. Many businesses make such claims despite lacking FDA approval for their stem cell products and absent convincing evidence from well-designed and appropriately powered controlled clinical trials that their interventions are safe and efficacious. The three states with the largest concentrations of such clinics are California with 347 clinics, Florida with 333, and Texas with 310. Arizona, with 119 clinics, is tied with New Jersey in having the fourth largest number of clinics.

(In 2021 the FDA wrote to 380 stem cell clinics with warning letters for them to stop their practices. Occasionally these clinics have caused blindness, bacterial infections and tumours etc…)

The only stem cell products that are FDA-approved for use in the United States consist of blood-forming stem cells (also known as hematopoietic progenitor cells) that are derived from umbilical cord blood.

Small differences in implementation of a protocol for sourcing and growing cells used in therapy can cause large differences in the quality of the cells. Two clinicians performing the same work, with the same protocol, in different clinics may produce widely varying outcomes for patients. This has been very evident in the delivery of mesenchymal stem cell therapies.

First generation mesenchymal stem cell transplants are quite good at suppressing chronic inflammation for a time, but increased regeneration is an unreliable outcome at best. In general, regeneration through cell therapy remains an elusive goal in the clinic.

As manipulation means any changes to or development from stem cells, clinics have sprouted outside the USA eg Panama, Bahamas, Costa Rica etc manipulating or claiming to manipulate stem cells for patient benefit. This can be areas such as harvesting your own stem cells, multiplying them in a dish, and then reinjecting many thousands more than before.

Or you can edit the germline ie the genome, eg at www.synthego.com, or bit.bio | synthetic biology | precision engineered human cells where single nucleotide or codons may be changed, tag insertions, and gene knockouts or knock ins (for disease modelling or protein tagging) using your own or the CRO supplied IPS cell lines, and can be ordered in pool or clone formats. So CRISPR edits are offered in IPSCs.

Companies can produce brain cells, (different types) muscles cells, some ready for experimentation as early as 2 days post revival and form functional neuronal networks at 17 days. (but are not available for general medical use in humans) For example see bit.bio | synthetic biology | precision engineered human cells

Germany recently led the world in the number of stem cell trials underway.

Therapeutic cloning, also called somatic cell nuclear transfer, is a technique to create versatile stem cells independent of fertilized eggs. In this technique, the nucleus, which contains the genetic material, is removed from an unfertilized egg. The nucleus is also removed from the cell of a donor.

This donor nucleus is then injected into the egg, replacing the nucleus that was removed, in a process called nuclear transfer. The egg is allowed to divide and soon forms a blastocyst. This process creates a line of stem cells that is genetically identical to the donor's cells — in essence, a clone.

Diet, exercise, sleep and stem cells

What you eat, (and your gut microbiome composition) how much exercise you get, and sleep, can all affect the effectivity of your stem cell population and stem cell bank.

4) Cautions about using stem cells, and what to know beforehand

When doing anything out of the ordinary, one should evaluate the risks and potential for damage and weigh this against the potential benefits.

Many clinics offering stem cell treatments make claims that are not supported by a current understanding of science.

In the USA, the US Food and Drug Administration (FDA) regulates regenerative medicine products. There continues to be broad marketing of unapproved products considered regenerative medicine therapies that are intended for the treatment or cure of a wide range of diseases or medical conditions. These products require FDA licensure/approval to be marketed to consumers. Before approval, these products require FDA oversight in a clinical trial. These unapproved products whether recovered from your own body or another person’s body, include stem cells, stromal vascular fraction (fat-derived cells), umbilical cord blood and/or cord blood stem cells1, amniotic fluid, Wharton’s jelly, ortho-biologics, and exosomes. FDA has received reports of blindness, tumour formation, infections, and more, detailed below, due to the use of these unapproved products.

Note: Even if stem cells are your own cells, there are still safety risks such as those noted above. In addition, if cells are manipulated after removal, there is a risk of contamination of the cells.

In March 2021, 1,480 U.S. businesses operating 2,754 clinics were found selling purported stem cell treatments for various indications. More than four times as many businesses than were identified 5 years ago are selling stem cell products that are not FDA-approved and lack convincing evidence of safety and efficacy.

But many clinics around the world manipulate or claim to manipulate stem cells. Hundreds of clinics are selling the unapproved treatments for arthritis, Alzheimer’s, COVID-19 and many other conditions. Some clinics may inappropriately advertise stem cell clinical trials without submitting an IND. Some clinics also may falsely advertise that FDA review and approval of the stem cell therapy is unnecessary. The only stem cell-based products that are FDA-approved for use in the United States consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood. These FDA-approved stem cell products are listed on the FDA website.

The majority of medical clinics that offer stem cell treatments administer mesenchymal stem cells (MSCs), which they source from human fat (adipose tissue) or bone marrow.

Stem cell therapy, or regenerative medicine, has resulted in life-saving treatment of patients with certain types of cancer and blood-related diseases, such as leukemia, lymphoma, and multiple myeloma. However, most stem cell products are, at present, investigational in nature, and their safety and efficacy continue to need testing in well-designed and rigorously conducted clinical trials.

Stem cells have tremendous promise to treat a range of diseases, injuries and other health-related conditions. Their potential is evident in the use of blood stem cells to treat diseases of the blood, a therapy that has saved the lives of thousands of children with leukemia; and can be seen in the use of stem cells for tissue grafts to treat diseases or injury to the bone, skin and surface of the eye. Important clinical trials involving stem cells are underway for many other conditions and researchers continue to explore new avenues using stem cells in medicine.

The list of diseases for which stem cell treatments have been shown to be beneficial is still very short. The best-defined and most extensively used stem cell treatment is hematopoietic (or blood) stem cell transplantation, for example, bone marrow transplantation, to treat certain blood and immune system disorders or to rebuild the blood system after treatments for some kinds of cancer.

Without manipulation in the lab, tissue-specific stem cells can only generate the other cell types found in the tissues where they live. For example, the blood-forming (hematopoietic) stem cells found in bone marrow regenerate the cells in blood, while neural stem cells in the brain make brain cells. A hematopoietic stem cell won’t spontaneously make a brain cell and vice versa. Thus, it is unlikely that a single cell type can be used to treat a multitude of unrelated diseases involving different tissues or organs.

Be wary of clinics offering treatments with stem cells originating from a part of your body unrelated to your disease or condition.

Embryonic stem cells and iPS cells, however, are not good candidates to be used directly as treatments, as they require careful instruction to become the specific cells needed to regenerate diseased or damaged tissue. If not properly directed, these stem cells may overgrow and cause tumours when injected into the patient.

View clinics that offer the same cell treatment for a wide variety of conditions or diseases with extreme caution. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.

Cells from your own body are not automatically safe when used in treatments

In theory, your immune system would not attack your own cells if they were used in a transplant. The use of a patient’s own cells is called an autologous transplant. However, the processes by which the cells were acquired, grown and then reintroduced into the body would carry risks. Here are just a few known risks of autologous stem cell treatments:

· Any time cells are removed from your body, there is a risk they may be contaminated with viruses, bacteria or other pathogens that could cause disease when reintroduced

· Manipulation of cells by a clinic may interfere with their normal function, including those that control cell growth

· How and where the cells are put back into your body matters, and some clinics inject cells into places where they are not normally present and do not belong

Every medical procedure carries risk; be wary of clinics that gloss over or minimize the risks associated with their treatments.

Questions to ask before stem cell therapy:

From the FDA website: If you're considering stem cell treatment in the United States:

Ask if the FDA has reviewed the treatment. Ask your health care provider to confirm this information. You also can ask the clinical investigator to give you the FDA-issued Investigational New Drug Application number and the chance to review the FDA communication acknowledging the IND. Ask for this information before getting treatment—even if the stem cells are your own.

Request the facts and ask questions if you don’t understand. To participate in a clinical trial that requires an IND application, you must sign a consent form that explains the experimental procedure. The consent form also identifies the Institutional Review Board (IRB) that assures the protection of the rights and welfare of human subjects. Make sure you understand the entire process and known risks before you sign. You also can ask the study sponsor for the clinical investigator’s brochure, which includes a short description of the product and information about its safety and effectiveness.

If you're considering treatment in another country:

Learn about regulations that cover products in that country.
Know that the FDA does not have oversight of treatments done in other countries. The FDA typically has little information about foreign establishments or their stem cell products.
Be cautious. If you’re considering a stem cell-based product in a country that may not require regulatory review of clinical studies, it may be hard to know if the experimental treatment is reasonably safe.

Questions to ask the clinic before treatment:

Is the treatment routine for this specific disease or condition?
Is the treatment part of a formal clinical trial? Learn more about things to consider with clinical trials here.
What are the alternative treatment options for my disease or condition?
If I have this treatment, could it affect whether I get into a clinical trial in the future?
What are the possible benefits I can expect? How will this be measured and how long will this take?
What other medications or special care might I need?
How is this stem cell procedure done? Consider these nine things to know about stem cell treatments.
- What is the source of the stem cells?
- How are the stem cells identified, isolated and grown?
- Are the cells differentiated into specialized cells before therapy?
- How are the cells delivered to the right part of the body?
- If the cells are not my own, how will my immune system be prevented from reacting to the transplanted cells?
What is the scientific evidence that this new procedure could work for my disease or condition? Where is this published?
Have there been (earlier) clinical trials? What was learned from these trials?
Is there independent oversight of the treatment plan by an ethics committee?
Is there any independent oversight or accreditation of the clinic where the treatment will be done and the facility where the cells are processed?
Is there approval from a national or regional regulatory agency, such as the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA) or Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), for this treatment of this specific disease?
What are the risks of the procedure itself, and the possible side effects both immediate and long-term?
Are there any other risks to me in joining in the study?
What will be done if an adverse reaction (bad side-effect) develops? Who is the person to contact in an emergency or research-related injury? Who will provide emergency medical care?
Is the clinic adequately prepared to handle emergencies such as a serious allergic reaction?
What follow-up treatment will be received, and for how long? What will I need to do?
Who is the doctor in charge of the treatment? What specialized training does this doctor have? How well trained are the other doctors and the technical support staff?
How many people have been treated for my disease or condition at your clinic? Of those, how many have gotten better? How many haven’t? Have your findings been published?

Or questions on a more general front:

Treatment:

· What possible benefits can the patient get from stem cell therapy? How can these be measured and how long will it take?

· Are there other medications or special care the patient needs aside from the treatment?

· Which stem cell source best fits the patient’s condition?

· What are other treatment options for the patient’s condition?

· What is their stem cell procedure (from harvesting to follow-up check-up)?

Safety and Emergencies

· If the patient is given donor stem cells, what are the success and failure rates of the therapy?

· What are the possible long-term side effects of the treatment?

In case a side effect develops, what do stem cell centers do, who will the patient reach out to, and how immediate can they respond to the side effect?
How experienced are the doctor and the support staff who will perform the procedure?
How advanced and sterilized is the clinic’s equipment?

Costs

· What are the expenses for stem cell therapy?

· What other costs will the patient incur?

Patient’s Rights

· What are the patient’s rights (confidentiality, update for new information, and the right to withdraw from the procedure)?

· What compensation will the patient be entitled to in case they will get injured while on the treatment process?

5) What and where are stem cell therapies in use today eg clinics; what are the potential benefits; and risks, and should one cyrobank some stem cells?

As mentioned above, in March 2021, 1,480 U.S. businesses operating 2,754 clinics were found selling purported stem cell treatments for various indications. More than four times as many businesses than were identified 5 years ago are selling stem cell products that are not FDA-approved and lack convincing evidence of safety and efficacy.

Today, according to bioinformant, the majority of medical clinics that offer stem cell treatments administer mesenchymal stem cells (MSCs), which they source from human fat (adipose tissue) or bone marrow (likely taken from the hip).

Mesenchymal stem cells are a type of multipotent stem cell that is administered for a range of medical applications, including orthopedic repair, pain management, arthritis, and asthma.

When properly administered, multipotent self-derived stem cells (such as MSCs) may be safe for patient use.

Stem cell transplants are used to treat conditions in which the bone marrow is damaged and is no longer able to produce healthy blood cells.

Transplants can also be carried out to replace blood cells that are damaged or destroyed as a result of intensive cancer treatment.

Conditions that stem cell transplants can be used to treat include:

severe aplastic anaemia (bone marrow failure)
leukaemia – a type of cancer affecting white blood cells
lymphoma – another type of cancer affecting white blood cells
myeloma – cancer affecting cells called plasma cells
certain blood, immune system and metabolic disorders – examples include sickle cell anaemia, thalassaemia, severe combined immunodeficiency (SCID) and Hurler syndrome

A stem cell transplant will usually only be carried out if other treatments have not helped, the potential benefits of a transplant outweigh the risks and you're in relatively good health, despite your underlying condition.

The UK NHS describes this below.

A stem cell or bone marrow transplant is a long and complicated process that involves 5 main stages.

These stages are:

1. Tests and examinations – to assess your general level of health.

2. Harvesting – the process of obtaining the stem cells to be used in the transplant, either from you or a donor.

3. Conditioning – treatment to prepare your body for the transplant.

4. Transplanting the stem cells.

5. Recovery – you'll need to stay in hospital for at least a few weeks until the transplant starts to take effect.

There are 3 main ways stem cells can be harvested, these are:

from blood – where the stem cells are removed from your blood using a special machine
from bone marrow – where a procedure is carried out to remove a sample of bone marrow from the hip bone
from cord blood – where donated blood from the placenta and umbilical cord of a newborn baby is used as the source of stem cells (find out more from the NHS Cord Blood Bank)

Stem cells produced by bone marrow that can turn into different types of blood cells.

The 3 main types of blood cell they can become are:

red blood cells – which carry oxygen around the body
white blood cells – which help fight infection
platelets – which help stop bleeding

A stem cell transplant involves destroying any unhealthy blood cells and replacing them with stem cells removed from the blood or bone marrow.

It may be possible to remove stem cells from your own blood or bone marrow and transplant them later after any damaged or cancerous cells have been removed.

If this isn't possible, stem cells from a donor's blood or bone marrow will usually be used.

Removing stem cells from blood

The most common way to harvest stem cells involves temporarily removing blood from the body, separating out the stem cells, and then returning the blood to the body.

To boost the number of stem cells in the blood, medication that stimulates their production will be given for about 4 days beforehand. On the fifth day, a blood test will be carried out to check there are enough circulating stem cells.

If there are enough cells, veins in each arm will be connected by tubes to a cell-separator machine. Blood is removed from one arm and passed through a filter, before being returned to the body through the other arm.

This procedure isn't painful and is done while you're awake. It takes around 3 hours and may need to be repeated the next day if not enough cells are removed the first time.

Removing a bone marrow sample

An alternative method of collecting stem cells is to remove around a litre of bone marrow from your hip bone using a needle and syringe. However some clinics treating specific issue eg cartilage issues, can take only 60 to 100 ml of bone marrow, a tiny proportion of the bone marrow. The bone marrow extract is said to have much greater efficacy and yield than other approaches.

The needle may need to be inserted into several parts of your hip to ensure enough bone marrow is obtained. This is done under a general anaesthetic, so you'll be asleep and won't feel any pain while it's carried out.

However, the area where the needle is inserted may be painful afterwards and you'll have marks on your skin where the needles were inserted (usually one on each side).

Many people are well enough to leave hospital between 1 and 3 months after the transplant. If donated stem cells were transplanted, you'll also usually need to take medicines that stop your immune system from working so strongly, to reduce the risk of your body attacking the transplanted cells (immunosuppressants), or to reduce the risk of the transplanted cells attacking other cells in your body.

Cord blood (umbilical cords often discarded when a baby is born)

Blood-producing stem cells (called haematopoietic stem cells) are present in cord blood. These cells are what we call 'unspecialised', which means that they have the ability to develop into those parts of the blood that the patient's body requires; whether red blood cells, white blood cells or platelets.

Cord blood transplants have been shown to cure patients with a variety of serious conditions:

Malignancies:

cancers of the blood, e.g. Leukaemia, lymphoma.

Bone marrow failure:

when bone marrow doesn't produce the cells it should.

Haemoglobinopathies:

blood disorders such as sickle cell anaemia or thalassaemia.

Immunodeficiencies:

when the immune system doesn't work properly.

Metabolic disorders:

these affect the breakdown of waste products in the body.

The risks of a stem cell / bone marrow transplants are outlined at Stem cell and bone marrow transplants - Risks - NHS (www.nhs.uk)

Costs:

When properly administered, multipotent self-derived stem cells (such as MSCs) can be safe for patient use.

Clinics often charge between US$2,000 to $25,000 for adult stem cell injections and other infusions which they advertise for an assortment of diseases, including diabetes, autism, cancer, multiple sclerosis and vision problems. Some clinics use stem cells derived from fat, harvested via liposuction then reinjected into patients, aiming to repair joints or fight disease. Others use bone marrow or blood taken from umbilical cords after birth.

Attendees at a 2016 FDA public workshop discussed several cases of severe adverse events. One patient became blind due to an injection of stem cells into the eye. Another patient received a spinal cord injection that caused the growth of a spinal tumor.

Other potential safety concerns for unproven treatments include:

Administration site reactions, and infections;
The ability of cells to move from placement sites and change into inappropriate cell types or multiply;
Failure of cells to work as expected, and
The growth of tumours.

FDA has mailed many warning letters to clinics. According to a paper published in the journal Cell Stem Cell, at least 351 businesses offer “unproven” stem cell interventions from clinics spread across the U.S.

The FDA’s Center for Biologics Evaluation and Research (CBER) regulates human cell and tissue-based products in the U.S., known as “HCT/Ps.” The FDA has two different paths for cell therapies based on relative risk.

These pathways are commonly called “361” and “351” products.

The 361 products that meet all the criteria in 21 CFR 1271.10(a) are regulated as HCT/Ps and are not required to be licensed or approved by the FDA. These products are called “361 products” because they are regulated under Section 361 of the Public Health Service (PHS) Act.

If a cell therapy product does not meet all the criteria outlined in 21 CFR 1271.10(a), then it is “regulated as a drug, device, or a biological product under the Federal Food, Drug, and Cosmetic Act (FDCA) and Section 351 of the PHS Act.”

These “351” products require clinical trials to demonstrate safety and efficacy in a process that is nearly identical to that what is required for pharmaceutical products to enter the marketplace.

Stem cell centers must ensure that their treatments meet the FDA’s criteria to be classified as “351” products.

And the clinics offerings:

Source: The American Stem Cell Sell in 2021

Legitimate clinics?:

Source: 2021: What Stem Cell Clinics Do You Trust? | BioInformant

According to bioinformant, each clinic listed below has treated large populations of patients with adult stem cells. At least one (Regenexx) is maintaining a Patient Registry to document long-term patient outcomes.

1. GIOSTAR (Chicago / San Diego)

The Global Institute of Stem Cell Therapy and Research (GIOSTAR) (Chicago / San Diego) provides adult stem cells for autologous (ie your own) and allogeneic (ie other peoples) stem cell therapy, based on research by Dr. Anand Srivastava. Dr. Anand Srivastava: Summary - GIOSTAR Chicago This stem cell treatment group offers treatments for a range of chronic conditions, musculoskeletal injuries, and degenerative diseases.

GIOSTAR states they can treat joint pain (knees, shoulders, hips), orthopedic injuries, arthritis, lung diseases, hair loss, erectile dysfunction, autoimmune diseases, and post-COVID complications. It can also provide anti-aging and aesthetic treatments, including IV vitamin therapy.

Each of GIOSTAR’s clinics is licensed for the application of stem cell therapy. Since 2000, its team of scientists and clinicians have been developing and utilizing stem cell-based clinical protocols for the purpose of stem cell treatment.

Within the United States, GIOSTAR treats patients at its Chicago, IL, location. It also serves clients at its clinical sites based in Mexico, India, Brazil, Thailand and U.A.E.

GIOSTAR claims that it is is one of the world’s most established stem cell treatment providers, having treated thousands of patients over the past 21 years.

2. Stem Cell Institute (Panama)

From website: Founded by Dr. Neil Riordan, said by some to be a globally recognized stem cell expert, the Stem Cell Institute in Panama is among the world’s leaders in stem cell research and therapy. Their treatments focus on well-targeted combinations of allogeneic umbilical cord stem cells, as well as autologous bone marrow stem cells.

The stem cells clinic uses stem cell therapies to treat various ailments, including the following:

· spinal cord injury (SCI)

· rheumatoid arthritis

· heart failure

· osteoarthritis

· multiple sclerosis

· autoimmune diseases

· genetic disorders, such as autism and cerebral palsy

. Stem Cell Therapy for MS:

One of their most recent studies exhibited the clinical feasibility of stem cell transplant process as a safe and effective treatment approach for patients with multiple sclerosis (MS).

Published in the Journal of Translational Medicine, the study showed that umbilical cord stem cells can slow down MS disease progression and decrease the frequency of flare-ups.

However, these stem cells did not exhibit the ability to repair damaged nerve cells or myelin sheaths.

Clinical Trials Results

After the completion of this clinical study, there was an improvement in MS patient disability. The 1-month mark of the study documented improvements in mobility, hand, bladder, bowel, and sexual functions. Importantly, the study demonstrated that a sustained one-year umbilical cord stem cell therapy has more durable benefits than current MS drug therapies.

A number of celebrities have visited his clinic in Panama eg Mel Gibson took his Father there, and claimed positive results, whilst some in the stem cell community are sceptical of the efficacy of results.

3. Regenexx (Denver, Cayman Islands & more) (Orthopedic specialists)

Headquartered in Denver, CO, Regenexx offers self-derived (autologous transplant) same-day stem cell treatments to patients with orthopedic injuries and conditions. Regenexx clinics incorporate a variety of regenerative approaches, drawing patients from all over the U.S. who are seeking innovative, non-surgical treatments.

Regenexx claims it has more than 60 clinic locations worldwide.

Regenexx Stem Cell Technology

The Regenexx® technology involves a procedure in which a small bone marrow sample (likely from your hip) is extracted through a needle and blood is drawn from a vein in the arm. These samples are then processed in a laboratory and the cells they contain are injected into the area needing repair, with the goal of delivering large numbers of stem cells to the site of injury.

Beyond FDA-Approved Cell Therapy

Regenexx is also a licensed offshore clinic in the Cayman Islands Stem Cell Therapy Procedures | Regenexx Cayman where patients can undergo treatments that utilize laboratory-expanded (“ex vivo”) stem cell populations. This approach allows for a much larger number of stem cells to be administered to the patient than is supported by U.S. law, which currently prohibits laboratory procedures that the FDA considers to exceed “minimal manipulation.” (At Regenexx Cayman, they state they grow your stem cells up to 100 to 1,000 times more than other procedures).

They will also bank your stem cells for future use ($250 a year).

Dr. Christopher Centeno is the Founder and CEO of Regenexx. He is a global authority in the culture expansion and clinical use of adult stem cells to treat orthopedic injuries and the visionary behind the Regenexx® technology.

A Regenexx patient wrote about their experience: read my experience.

4. DVC Stem (Cayman Islands)

Headquartered in Seven Mile Beach, Grand Cayman, physicians at DVC Stem have been using complimentary alternative therapies to clinically treat patients with various medical conditions. It is one of the most advanced stem cell clinics in the Caribbean, with IRB-approved protocols, a fully licensed staff, and a facility that is accredited by the medical governing bodies of the Cayman Islands.

DVC Partner Lab, Vitro Biopharma

DVC Stem sources its cells from its partner lab Vitro Biopharma Inc, a state of the art, US-based, FDA registered, cGMP compliant and ISO 9001 certified laboratory, and only use American Association of Tissue Bank (AATB) certified suppliers of full-term, ethically U.S.-donated human umbilical cords.

Led by Medical Director Louis A. Cona, MD, DVC Stem’s focus is on cord-tissue derived allogeneic stem cell therapy for degenerative conditions, wear and tear, and intelligent aging.

Notable patients the company has treated include Lou Ferrigno (champion bodybuilder/actor), Michael Armand Hammer (businessman/philanthropist), and David Lyons (Founder, MS Fitness Challenge), and others .

5. Okyanos (Bahamas)

Founded in 2011, Okyanos is a stem cell therapy provider that specializes in treating patients with congestive heart failure (CHF) and other chronic degenerative conditions. Okyanos Cell Therapy uses internationally-approved technology to deliver a mixed population of fat (adipose) derived stem and regenerative cells (ADRCs) (autologous) to patients with conditions such as the following:

· cardiovascular disease

· orthopedic issues

· neurological disorders

· urological indications

· autoimmune conditions

Stem Cell Treatment Centers

Okyanos maintains both a North American Office in Clearwater, FL, and a purpose-built Cell Therapy Surgical Center in Freeport, Grand Bahama. Okyanos’ stem cell treatments are performed in their state-of-the-art surgical centers under the care of board-certified doctors.

Okyanos is also fully licensed and regulated under the Bahamas Stem Cell Therapy and Research Act and adheres to U.S. surgical center standards. A funder of the clinic is Edward Bosarge. Click here to read our interview with Matthew Feshbach, Co-Founder and CEO of Okyanos.

6. Celltex (Houston, TX)

Celltex states that it specializes in cryopreserving mesenchymal stem cells (MSCs) for therapeutic use. Celltex acquires stem cells by collecting a small fat sample from a patient, from which MSCs are extracted, isolated, multiplied, and stored for future use (known as cell banking).

Patients can then use their stored stem cells for regenerative purposes through infusions or injections performed by a licensed physician.

FDA-Approved Stem Cell Clinical Trials

Because the FDA considers an individual’s stem cells a drug if they have been expanded in large quantities, Celltex has begun the process of undertaking clinical trials on stem cells as a treatment for a range of medical conditions, seeking approval from the FDA to allow physicians to utilize these cells.

Approved Stem Cell Therapies in Mexico

Nonetheless, to meet the immediate needs of its clients, the company also has taken steps to meet the requirements of the FDA and COFEPRIS, a Mexican institution equivalent to FDA in MSCs import and export.

Celltex also works with Mexican hospitals that are established and certified that allowed the company’s cell-banking clients to receive their stem cells for medical purposes.

7. Opus Biological, (London, UK) Home - Opus Biological

We understand that Opus Biological in London is the only UK clinic permitted by the regulators to culture stem cells in the UK. Dr David Porter specialised in treating sportspeople /athletes, and focusses on MSCs drawn from bone marrow aspiration, (60 to 100ml is extracted- a tiny proportion of the bone marrow, then cultured to at least 40 million stem cells) and reinjected, with a specialty in orthopaedics and osteoarthritis. Also does Platelet rich plasma treatment (PRP) using a patient’s own blood to encourage the healing of injured joints, muscles, tendons, and ligaments.

Last count there were 74 stem cell clinics in the UK.

8. Stemaid, (San Jose del Cabo, Baja, Mexico) Stemaid Institute - Pluripotent Stem Cell Therapy

This is the only clinic I am aware of that will offer pluripotent / embryonic stem cell injections.

There offering is wide and a number of people I know have been there and have gone back a second time.

Stem Cell cryobanking – long term storage

As stem cells “age” and become less effective the older you get (possibly through environmental damage) some make a case for extracting stem cells from your body when you are younger- and the stem cells are more potent and in better shape) and freezing them and holding them in reserve for unfreezing when you are older and may need them.

Stem cells can be harvested from one of the procedures outlined above.

Many people cryofreeze their newborn childs umbilical cord, with many companies providing the service eg UK's Leading Umbilical Cord Blood Stem Cell Bank | Cells4Life ; or in the USA companies like Lifebank USA: Home - Lifebank Stem Cell Banking (lifebankusa.com) .

The sales pitch is pay them to cryobank your babys cord stem cells, and maybe one day (they do not know how to do this at present) you will be able to repair damaged tissue; regrow and replace worn out organs, or cure life threatening diseases. It is unclear if the frozen stem cells can be correctly unfrozen and then used.

If you did not have this done at birth then one needs to take them from the blood or from the bone marrow, or maybe from teeth- before you lose all of your “baby teeth”.

See also What Is Stem Cell Banking? | Future Health Biobank Stem cell banking offers the opportunity to have your precious cells cryogenically frozen for over 25 years, ready for future use should they be required. Umbilical cord blood, cord tissue and dental tooth pulp are rich sources of these amazing cells. At present, cord blood stem cells can be used in therapies and transplants to treat over 85 diseases, including leukaemias, bone marrow cancer, lymphomas and anaemias. For a full list see: Diseases Treated Using Umbilical Cord Stem Cells | Future Health Biobank In addition, there are over 5,000 clinical trials that use stem cell therapies.

In January 2022, more than 70% of the global cord blood market is controlled by the world’s 12 largest cord blood banking operators. According to ClinicalTrials.gov, there are at least 1,200 clinical trials evaluating the use of cord blood stem and progenitor cells. These studies use unmanipulated whole cord blood (total nucleated cells/TNC), mononuclear cells (MNC), or cord blood-derived mesenchymal stem cells (MSCs). These studies are targeting clinical indications that range from pulmonary diseases to infertility to orthopedic conditions, but the most common area of research is neurologic conditions—such as cerebral palsy, autism, stroke, and hypoxic ischemic encephalopathy. Although cord blood is now used to treat 80 different diseases, this number will expand as regenerative medicine applications begin to receive approvals in major healthcare markets worldwide. (See bioinformant website)

A list of FDA clinical trials can be found on Search of: "mesenchymal stem cell" OR "mesenchymal stem cells" OR "mesenchymal stromal cell" OR "mesenchymal stromal cells" - List Results - ClinicalTrials.gov

Or you can, as an adult, get your stem cells stimulated to be released in to your blood and then collected and frozen. (There are normally only a small number of stem cells in your blood). A description of such a process is given on a South florida clinic website Umbilical Cord Blood Banking California | Adult Stem Cell Therapy Texas | Stem Cell Storage Boston (stemcellimmuneregenerative.com) (to raise the number of stem cells in your bloodstream, you'll get injections (shots) of a medication called granulocyte colony-stimulating factor, or GCSF. GCSF helps your body make more stem cells than usual. It also helps the stem cells move into your bloodstream, where they're easier to harvest. A special medication called Neupogen (Filgrastim, sold under the brand name Neupogen among others, is a medication used to treat low neutrophil count. Filgrastim is used to treat neutropenia -low white blood cells- , stimulating the bone marrow to increase production of neutrophils. It is a synthetic (man-made) form of a substance that is naturally produced in your body called a colony stimulating factor. Filgrastim helps the bone marrow to make new white blood cells. Causes of neutropenia include chemotherapy and bone marrow transplantation) works to "trick" your bone marrow into over-producing stem cells so that they can be collected from your blood through the use of a central venous catheter. Neupogen is given in very high doses as a daily shot (injection); may also receive NEUPOGEN after a bone marrow or stem cell transplant, to help speed up your recovery.

Some studies have shown that a specific regime followed in a course of Hyperbaric Oxygen Therapy may also substantially boost the number of stem cells in your body.

Others believe that there are various natural ways to boost stem cell production, such as intermittent fasting / calorie restriction, exercise etc.

Bone Marrow Transplants:

Healthy marrow and blood cells are needed to live. When disease affects marrow so that it cannot function properly, a marrow or cord blood transplant could be the best treatment option, and for some patients, offers the only potential cure.

A bone marrow transplant takes a donor’s healthy blood-forming cells and puts them into the patient’s bloodstream, where they begin to grow and make healthy red blood cells, white blood cells and platelets. Patients receive high doses of chemotherapy to prepare their body for the transplant. Then on transplant day, the patient receives the donated cells in a process that is like getting blood or medicine through an intravenous (IV) catheter, or tube.

See also the previous section on stimulating the production of stem cells.

For further information see Learn the Basics of BMT | Be The Match - the majority of people they treat have blood cell disorders. Or www.bethematch.org

If you're thinking of ordering a DNA profile, you should do it before a stem cell transplant, as the DNA profiles may change after the transplant. As a bone marrow recipient, your blood cells will contain the DNA from your marrow donor, while your epithelial cells contain your own DNA. It is unclear how long this situation persists.

Spinal Treatments

When osteoarthritis affects the spine, it is known as spondylosis.

Application of stem cells in the repair of intervertebral disc degeneration:

With the acceleration of population aging, the incidence of spinal degenerative diseases has increased significantly, and the main sign is chronic low back pain, which seriously affects patients' quality of life and increases the economic burden on their family and society. Although the aetiologies of spinal degenerative diseases are varied and complex, intervertebral disc degeneration (IDD) is recognized as one of the most important causes. Degenerative disc diseases (DDDs) arising from IDD comprise a series of painful spinal diseases that include discogenic low back pain and lumbar disc herniation. At present, most patients use rest or conservative treatment for pain relief, as well as a variety of drugs such as steroids, local anaesthetics, and other blocking agents. When these methods are ineffective, surgery is often performed to relieve symptoms and improve quality of life. Surgical treatments can also solve pain problems, but have disadvantages such as inability to replace decreased nucleus pulposus (NP) cells, inability to reverse the pathological state of the intervertebral disc (IVD), and potential to cause various intraoperative and postoperative complications.

In recent years, with the rapid development of stem cell technologies that have been effectively applied in haematology, circulation, orthopaedics, and other fields, stem cells have attracted the attention of researchers and clinicians. With in-depth studies on the IVD and IDD as well as its mechanism, many teams have found that combination of stem cell technology and treatment for IDD can not only maintain the normal physiological function and structure of the IVD, but even reverse the IDD cascade. Organic combination of the IVD and stem cell technology has outstanding advantages for IDD treatment and recovery, but remains controversial.

Although cell therapy appears to have great potential for IVD regeneration, there remains a lack of relevant evidence regarding safety, long-term complications, effectiveness in different patient populations, and surgical cost-effectiveness. Further development of stem cell technology and in-depth exploration of IDD in the medical community will determine the future development direction of the organic combination of stem cells and IDD research. First, we need to further explore the interactions between stem cell repair mechanisms and target cells, and strive to identify more targets that promote differentiation. Second, we need to find ways to improve the harsh microenvironment in IDD to provide a better living environment for loaded stem cells. Third, we need to establish methods that can induce and differentiate stem cells from different sources more efficiently and stably, thereby improving the safety of stem cell application. Last, but not the least, it is necessary to optimize the performance of stem cell carrier materials to avoid secondary damage during implantation and further enhance the repair ability of stem cells.

The vertebral column provides protection to the spinal cord that runs through its central cavity. Between each vertebra is an intervertebral disc. The discs are filled with a gelatinous substance, called the nucleus pulposus, which provides cushioning to the spinal column.

But the intervertebral disc is made up of two components: the thick outer ring of fibrous cartilage called the annulus fibrosus, and thenucleus pulposus. The annulus fibrosus is the outer portion of the disc. It is composed of layers of collagen and proteins, called lamellae. This surrounds a more gelatinous core known as the nucleus pulposus; the nucleus pulposus is sandwiched inferiorly and superiorly by cartilage end-plates.

Osteoarthritis & Cartilage

Osteoarthritis (OA) is an age related joint disease associated with degeneration and loss of articular cartilage. Consequently, OA patients suffer from chronic joint pain and disability. Weight bearing joints and joints that undergo repetitive stress and excessive 'wear and tear' are particularly prone to developing OA. Cartilage has a poor regenerative capacity and current pharmacological agents only provide symptomatic pain relief. OA patients that respond poorly to conventional therapies are ultimately treated with surgical procedures to promote cartilage repair by implantation of artificial joint structures (arthroplasty) or total joint replacement (TJR).

In the last two decades, stem cells derived from various tissues with varying differentiation and tissue regeneration potential have been used for the treatment of OA either alone or in combination with natural or synthetic scaffolds to aid cartilage repair. Although stem cells can be differentiated into chondrocytes in vitro or aid cartilage regeneration in vivo, their potential for OA management remains limited as cartilage regenerated by stem cells fails to fully recapitulate the structural and biomechanical properties of the native tissue. Efficient tissue regeneration remains elusive despite the simple design of cartilage, which unlike most other tissues is avascular and aneural, consisting of a single cell type.

Although stem cells can be differentiated into chondrocytes in vitro or aid cartilage regeneration in vivo, their potential for OA management remains limited as cartilage regenerated by stem cells fails to fully recapitulate the structural and biomechanical properties of the native tissue.

Chondroblasts are a type of immature cells whereas chondrocytes are a type of mature cells. The main difference between chondrocytes and chondroblasts is that chondroblasts secrete the extracellular matrix of the cartilage whereas chondrocytes are involved in the maintenance of the cartilage. A chondroblast is a cell which originates from a mesenchymal stem cell and forms chondrocytes while osteoblast is (biology|cytology) a mononucleate cell from which bone develops.

Chondrocytes, or chondrocytes in lacunae, are cells found in cartilage connective tissue. They are the only cells located in cartilage. They produce and maintain the cartilage matrix, which is a type of lake in which the chondrocytes swim. Given that normal articular cartilage is hypoxic, chondrocytes have a specific and adapted response to low oxygen environment. Chondroblasts are called chondrocytes when they embed themselves in the cartilage matrix, consisting of proteoglycan and collagen fibers, until they lie in the matrix lacunae.

Osteocytes are the longest living bone cell, making up 90–95% of cells in bone tissue in contrast to osteoclasts and osteoblasts making up ~5%. Osteocytes form when osteoblasts become buried in the mineral matrix of bone and develop distinct features.

Osteoprogenitor cells, also known as osteogenic cells, are stem cells located in the bone that play a prodigal role in bone repair and growth. These cells are the precursors to the more specialized bone cells (osteocytes and osteoblasts) and reside in the bone marrow.

The disc is avascular, and the disc cells depend on diffusion from blood vessels at the disc's margins to supply the nutrients essential for cellular activity and viability and to remove metabolic wastes such as lactic acid.

(Collagen type II has exhibited protective effects in suppressing NP cell degeneration through its anticatabolic, proanabolic and antiapoptotic effects, suggesting that it may be a promising therapeutic agent for the prevention and treatment of DDD.)

The main methods of OA treatment involve non-pharmacological, pharmacological and surgical measures with the aim of reducing pain and improving tolerance for functional activity. Non-pharmacological management includes moderate exercises to strengthen the muscles, weight loss and massage therapies.

New born Umbilical Cord Stem Cells

Some groups collect new born babies umbilical cords which are rich with stem cells and then propose to use them in treatments.

Since HUCT mesenchymal stem cells are immune system privileged, cell rejection is not an issue and Human Leukocyte Antigen (HLA) matching is not necessary.

6) What advances can we expect by when?

The range of diseases for which there are proven treatments based on stem cells is still extremely small. Disorders of the blood and immune system and acquired loss of bone marrow function can, in some cases, be treated effectively with blood stem cell transplantation.

Doctors have been transferring blood stem cells by bone marrow transplant for more than 50 years, and advanced techniques for collecting blood stem cells are now used clinically. Umbilical cord blood, like bone marrow, is often collected as a source of blood stem cells and is being used experimentally as an alternative to bone marrow in transplantation. Today, doctors routinely use stem cells that come from bone marrow or blood in transplant procedures to treat patients with cancer and disorders of the blood and immune system.

Stem cell researchers have conducted / are conducting > 7,000 clinical trials to investigate the application of stem cell treatments for hundreds of different conditions, many of which, up until this point, have been incurable. (Source: clinicaltrials.gov) For those currently recruiting or in progress (February 2022) there are over 1,600 clinical trials in progress, and >400 active studies that are no longer recruiting. Some of these should hopefully yield some excellent new therapies.

For a clinical trial to begin, as part of the FDA’s review, investigators must show how each product will be manufactured so the FDA can make sure appropriate steps are being taken to help assure the product’s safety, purity, and strength (potency). The FDA also requires sufficient data from animal studies to help evaluate any potential risks associated with product use.

The only stem cell-based products that are FDA-approved for use in the United States consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood.

These products are approved for limited use in patients with disorders that affect the body system that is involved in the production of blood (called the “hematopoietic” system). These FDA-approved stem cell products are listed on the FDA website. Bone marrow also is used for these treatments but is generally not regulated by the FDA for this use.

There is a lot of research being undertaken around the world, with a range of companies and research establishments - encompassing the usual suspects and more , eg Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM) - Stanford University School of Medicine | Institute for Stem Cell Biology and Regenerative Medicine | Stanford Medicine ; Harvard Stem Cell Institute (HSCI) ; King's College London - Stem Cell Research (kcl.ac.uk); Stem Cell Regenerative Medicine Network | Faculty of Medicine | Imperial College London; Welcome — Oxford Stem Cell Institute and hundreds of others…

Organoids- making new organs and tissues for your body, and organ engineering

IPSCs, or adult stem cells eg fat cells, that have been treated ie made younger, to become stem cells can then be turned in to other cells eg brain cells / neurons, or skeletal cells, ) see bit.bio | synthetic biology | precision engineered human cells if you want to order some) can then be grown in to “brains in a dish” (takes 17 days) bones, livers, lungs etc and then a range of things can be done to them, such as research or testing new pharmaceutical drugs on them for safety profiles – maybe better than mice as many mice treatments do not translate to human effects. Eventually whole organs will be able to be grown, eg take some of your fat cells and grow yourself a new liver…. Such is the power of stem cells.

Companies such as volumetric, Volumetric (volumetricbio.com) are building 3D bio printers to help assemble such organs.

Such organoids offer sometimes reasonable representation of our tissues but currently lack the complexity needed for optimal research. Often scaffolds are needed to help build a 3D structure, and given issues with this, some scientists have been experimenting in space- the ISS, to build structures that do not need scaffolds due to lack of gravity in space.

Brain organoids emerging from culture tanks are currently under 5mm so have <1/10,000th of the volume of a human brain, and have no sensory inputs to gather info from the outside world. Some humans neurons are transplanted in to living mice. At if these neurons become “conscious” a whole range of ethical issues will emerge.

However there are many hurdles to be surpassed for this to become a reality, perhaps 10 to 20 years or more away.

Here is a categorisation of different approaches to make organoids:

Source: Cell-Stem Cell. Design approaches for generating organ constructs. Belmonte. 2019 (Categorisation)

But it is complex, with factors to consider:

With each approach having different plusses and minuses (colour shade correlates with the level of advantage):

And how much organoid modelling that has been done for each organ, as reviewed in leading journals:

Over the last decade, advances in stem cell technology, material science, bio-engineering, and gene editing have enabled us to develop a wide selection of approaches for generating human organ constructs that can recapitulate organ architecture, functionality, and pathophysiology.

7) Summary

Depending on what you want to achieve, there are some stem cell therapies that are currently approved and can work well. There are a huge number of researchers looking at newer stem cell treatments and the promise for significant treatment breakthroughs in the not too distant future appears high, although much still needs to be discovered. However many stem cell clinics currently offer unproven treatments at present for a wide range of indications, either in the USA or abroad, where much caution needs to be exercised by anyone wanting to experiment with such treatments, especially given the range of risks, some of which can be related to a specific clinics operation, and even the operator used in the clinic.

But some people, such as those in pain, want to believe false claims given desperation to relieve various issues. The author only hopes that whatever the affliction someone is seeking a remedy for will have scientifically proven efficacy over coming years, and that the range of regeneration treatments from stem cells should broaden dramatically over coming years.

References:

1. Effect of aging on stem cells. Abu Shufian Ishtiaq Ahmed. 2017. DOI: 0.5493/wjem.v7.i

2. www.Clinicaltrials.gov

3. Fda.gov

4. What Stem Cell Clinics Do You Trust? | BioInformant

5. The Cost Of Stem Cell Therapy in 2022 | BioInformant

6. Cell Stem Cell. November 2021

7. Stem Cells, Bagnara ; Alviano / Bonsi 2020

8. The science of stem cells. Jonathan Slack, 2018

9. Stem cell and bone marrow transplants - What happens - NHS (www.nhs.uk)

10. McKinsey, 2020

11. www.mayoclinic.org