Arizona Advanced Medicine Clinic

Stem Cell Therapy 2016 - State of the Art

In July of 2015 I wrote an article for our website entitled: Stem cells – Fountain of Youth? Or scam of the century? I was not alone is questioning the value of stem cell therapies. A Google search using the terms “stem cell therapy scam” pulls up a multitude of articles (including ours), all warning about the potential for fraudulent treatments with titles like “The Shady Side of Embryonic Stem Cell Therapy” from Quackwatch, “Stem Cell Fraud: A 60 Minutes investigation” from CBS News and “Consumer Updates> FDA Warns About Stem Cell Claims”. My personal favorite was “Medicine’s Wild West – Unlicensed Stem-Cell Clinics in the United States.”

Putting “benefits” into the search box brings up an equal number of articles extolling the benefits of this treatment. And stem cell clinics are proliferating like yeast in a warm oven.

Clearly the final chapter is not yet written in the book of stem cell therapy.

Part of the controversy stems (to make a bad pun) from the fact that each of us has our own stem cells, that the health and vitality of stem cells diminishes as we get older and/or sicker. Nevertheless, using our own stem cells for therapy seems intuitively like a better idea than using someone else’s stem cells.

Using other people’s stem cells for therapy seems like a reasonable alternative if our own stem cells are not usable for whatever reason. We do, however, need to keep in mind that someone else’s stem cells are going to be immunologically different from our own. The concept of immunologic difference leads to some concerns about therapy:

  • Stem cells are more than likely immunogenic – in other words, can cause an immune response leading to rejection if injected into someone else’s body.[1], [2] They are said not to have the HLA antigens on their surface, so that in theory they are immunologically naïve. However, when bone marrow is infused in someone as treatment for leukemia, that patient first has their own bone marrow completely destroyed, and then has to stay on immunosuppressant medication for the rest of their life. That sounds to me as though the bone marrow derived stem cells are immunogenic. It seems reasonable to assume that adipose-derived stem cells may also be immunogenic.
  • Embryonic stem cells do not appear to induce immunologic reactions. However, they have been shown to induce tumor growth. Bad idea.
  • Induced pluripotent stem cells (fully differentiated cells persuaded to become stem cells through manipulation of culture medium) are different from regular cells in that they sometimes forget to turn off their “never stop dividing” genes. I’m not sure that I would be willing to take that risk if it were my body in question.
  • Blood transfusions have been done for years – with life-saving results. Nevertheless, even blood has to be typed and cross-matched – i.e. we have to make sure that the unit of blood is immunologically compatible with the person who receives it, so that we don’t get a major transfusion reaction leading potentially to death of the recipient. When our own blood is transfused back into us, there is no risk of death or illness from transfusion reaction.

So the question remains, why is all the focus now in “off the shelf” allogenic (derived from someone else) stem cell therapies? Why not use our own stem cells to treat our own bodies?

Do we have enough stem cells to affect our own healing?

Is it possible that we would actually need to transfuse more stem cells than we are able to generate spontaneously and still follow the FDA rules about stem cell therapy? The literature is full of articles detailing how to culture them and increase their numbers.

Stem cell therapy is increasingly used to improve joint function and relieve pain in patients with osteoarthritis.[3] In the past, transplantation of cartilage cells has been used, but required a surgical procedure to obtain the cartilage from a healthy joint and insert it into the affected joint. Nor was there any evidence that arthroscopic surgery provided any significant benefit to the patient.[4] Now we read increasing numbers of reports of successful therapy using mesenchymal stem cells simply injected into the arthritic joint without any manipulation or culturing, and with good therapeutic results.[5], [6]

What about the age factor?

We know that a lot of functions decline with age. It would seem reasonable to suspect that stem cell function also declines with age.

Indeed the influence of age on stem cells has also been studied. There is undoubtedly some age-related decline in stem cell function.[7] In this study “aged” was defined as derived from anyone over the age of 40. Osteoarthritis does not occur very often in people under the age of 40, so it is unclear how this factor might modify our treatment of the “elderly” with osteoarthritic joints, if they become “elderly” at their 40th birthday.

Use of “elderly” autologous vs “young” allogenic really depends on our concern for the immunologic potential of the allogenic cells.

We also read that stem cell numbers increase in numbers in arthritis joints, the increase being dependent on the severity of the disease. So do stem cells actually create the conditions under which osteoarthritis develops? Synovial fluid from osteoarthritic joints inhibits cartilage formation by mesenchymal stem cells from healthy donors.

Could the nutritional status of the body also be a factor? We know that people who eat fast food diets tend to die younger than people who eat Mediterranean diets. One study reports: “Among individuals aged 70 to 90 years, adherence to a Mediterranean diet and healthful lifestyle is associated with a more than 50% lower rate of all-causes and cause-specific mortality.”[8] It seems reasonable to conclude that the health of their stem cells might also be influenced by diet and lifestyle.

With that factor in mind, it also seems reasonable to conclude that if one modifies the health of one’s cells by improving one’s nutrition and decreasing one’s total toxic load, then the health of the stem cells might also improve, resulting in improved healing, and potentially in improved outcome if stem cell therapy becomes necessary.

As I have said in other articles, it would be ideal to be able to isolate the stem cells from adipose tissue (the so-called stromal vascular fraction) and then inject them directly either into a joint or into the blood stream. However, the FDA has declared that manipulating the adipose tissue in order to get a purified preparation of stem cells constitutes “more than minimal manipulation”, and therefore would have to go through a new drug application process along with payment of the “new drug application” fees – which are substantial – in the millions of dollars, when all is said and done. The FDA derives its funding from new drug application fees.

Clearly the individual patient sitting in our procedure room waiting for their stem cells to be re-injected is not going to be able to wait for a new drug application process to occur. So… we do the next best thing, and inject the adipose tissue (together with the stem cells which it contains) into the patient’s inflamed joint. It’s a little larger volume of fluid, but the stem cells end up where they are most needed in any case. Joint injection procedures do not fall under the jurisdiction of the FDA.

We feel that stem cell therapy has finally come to the point where it can be an office-based treatment for a multitude of illnesses. The most obvious of these is osteoarthritis, but once the stem cells are injected, their influence goes far beyond the joint into which they are placed. The growth factors which they induce can have far-reaching effects – we have barely tapped the surface of what stem cell therapy can do for healing.


[1] Cao J et al. Cells derived from iPSC can be immunogenic — Yes or No? Protein Cell. 2014 Jan; 5(1): 1–3.

[2] Scheiner Z, Talib S, Feigal EG. The Potential for Immunogenicity of Autologous Induced Pluripotent Stem Cell Derived Therapies. The Journal of Biological Chemistry, 289, 4571-4577 (February 21, 2014).

[3] Kristjánsson B, Honsawek S. Current Perspectives in Mesenchymal Stem Cell Therapies for Osteoarthritis. Stem Cells Int. 2014; 2014: 194318.

[4] Thorlund JB, Juhl CB, Roos EM, Lohmander LS. Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. Br J Sports Med. 2015 Oct;49(19):1229-35. doi: 10.1136/bjsports-2015-h2747rep.

[5] Perdisa F et al. Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence. Stem Cells International, vol. 2015, Article ID 597652, 13 pages, 2015. doi:10.1155/2015/597652.

[7] Stolzing A, Jones E et al. Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies. Mechanisms of Ageing and Development 129;3 (March 2008):163–173.

[8] Knoops KT et al. Mediterranean Diet, Lifestyle Factors, and 10-Year Mortality in Elderly European Men and Women - The HALE Project. JAMA. 2004;292(12):1433-1439. doi:10.1001/jama.292.12.1433.

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