This post is written in response to Dr. Peter Diamandis’s “Stem Cells are Poised to Change Health and Medicine Forever.” While this article was informative, I have taken the time to elaborate on some of the topics and discussed some inconsistencies with what we have seen in peer-reviewed scientific articles.
First, I wanted to elaborate on the definition of a stem cell that was presented in this article. Stem cells are defined as cells that are capable of both self-replication and differentiation into more specialized cell types. The article presents this idea as if all stem cells are created equal, however this not the case. Stem cells are classified by their potency or the breadth of their ability to differentiate into different cell types. At the top of this pyramid, we have the totipotent stem cells. These cells are able to differentiate into all of the different cell types necessary to create a human being including extraembryonic or placental cells. The only true totipotent cells are the fertilized egg through the first 16 cells in human development, then, these cells begin to differentiate. On the next level, we have pluripotent stem cells. These stem cells are capable of differentiating into cells in any of the three germ layers (endoderm, mesoderm, ectoderm), but are not capable of creating the placenta. Further down the differentiation chain we have multipotent stem cells. These cells are more specialized than pluripotent cells and are generally only able to differentiate into a few discrete cell types. Most of your adult stem cell population falls under this category, including mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs).
The article then discusses autologous adult stem cells sourced from adipose tissue. Adipose derived MSCs are significantly regulated by the FDA for a variety of reasons. First, an enzymatic degradation step is required to isolate the cells from the adipose tissue, which goes beyond the definition of minimal manipulation. Therefore, isolating these cells in this manner means that they would be regulated like a drug. Additionally, you then run into issues of homologous use, another hiccup with the FDA, when redelivering these cells back to the patient, again leading to a drug classification.
An alternative source for autologous adult stem cells is bone marrow aspirate. While adipose tissue has a higher percentage of MSCS compared to the overall cell population, bone marrow aspirate has a much higher cell density and contains almost as many MSCs by volume. The cells from bone marrow can then be concentrated, using centrifugation to enrich the concentration of MSCs at the point of care. This type of therapy would be regulated solely under section 361.
The article also brings up concerns about using the patient’s own stem cells, citing that with age comes genetic mutation, which would lead to a subpar treatment. While it is accepted that there will be some occasional random mutations as the cells age, there are many biological mechanisms in place to correct these types of mutations. If these random mutations were so severe that your adult stem cell population was rendered inactive, then you would be in serious trouble. So, this concept that genetic mutation builds as you develop, rendering these cells useless is incorrect. While the affectivity of a single cell doesn’t necessarily decrease, the concentration of stem cells in the bone marrow may decrease with age. Simply taking a larger volume of aspirate and concentrating it to the same final volume using centrifugation can fix this. One of our earlier blog posts by Dr. Richard Suzuki outlines a study that examines stem cells from patients over the age of 85.
Non-autologous sources of stem cells, like umbilical cord or placenta-derived cells, are only approved for use in a first or second-degree relative of the donor. The idea behind utilizing these cells is that because the stem cells are younger they are , therefore they are better. While this makes sense in theory, studies have shown that the mother’s stem cells are present in this tissue as well and quickly outcompete the stem cells of the baby . Additionally, you have problems with minimal manipulation when isolating, and homologous use when redelivering, these cells.
Finally, when Dr. Diamandis discusses current successes in stem cells I would like to point out that the study by Kohji Nishida actually deals with an entirely different type of stem cell population. Some of the work by Dr. Nishida employs the use of induced pluripotent stem cells (iPSCs). These are skin cells that have been exposed to four transcription factors that induce pluripotency in these cells. Currently there are no FDA approved therapies involving iPSCs for any applications. Some argue that this conversion from terminally differentiated cells to iPSCs may actually alter the genome and behavior of these cells in unpredictable ways, I think that this is more likely to cause detrimental damage than the natural aging process Dr. Diamandis expresses so much concern about in the beginning of his article. While there are great breakthroughs in this technology and research coming from Dr. Nishida’s lab, there is a lot of regulatory red tape to go through before any of these can be successfully translated into therapies in the US.
The real problem with the focus on Dr. Nishida’s work is that it may lead the reader to believe that iPSC technology is the closest to the clinic or most promising of stem cell technologies. This could not be more incorrect. Other recent success stories with stem cells worth noting range from healing non-union fractures, tendon repair, degenerative disc disease, and rotator cuff repair. With regards to degenerative disc disease, patients were injected with bone marrow concentrate and saw 70% improvement in pain and disability scores through two years, and an 86% improvement if they were treated with greater than 2000 MSCs per cc. This treatment allowed 81% of patients to avoid surgical intervention (fusion) for two years. In another study, when injecting BMCs during a rotator cuff repair, they saw 100% healing at 6 months compared to 67% of the control as measured by ultrasound. At the 10 year follow up, 87% of the patients treated with BMC had intact rotator cuffs compared to 44% of the control patients.
Dr. Diamandis did highlight some very exciting works in the stem cell field, which I support. But I hope that I have spoken to enough of the real, current, clinical uses of stem cells to show that stem cells are not poised to change the world of medicine forever, they are already doing it.