MSCs and other stem cells offer remarkable potential but our understanding of their science and medical applications is not ready for unregulated, widespread use. The complexity of tissue repair and cell replacement makes it clear that the proliferation of questionable “stem cell clinics” and off-shore medical tourism offices promoting their autologous “stem cell treatments” of unknown and unproven efficacy will not solve patient maladies in a meaningful way. The divergence between reputable clinical trials and the premature marketing of stem cell products to the public has broadened the gap and led to confusion in the press as highlighted by Galipeau et al.15 There are over 700 clinics offering direct-to-consumer marketing of “stem cell” treatments.16 We cannot support or recommend any treatment utilizing MSCs that does not use characterized cell product, maintain accurate records, measure intermediate parameters, predetermined surrogate endpoints and track and report final patient outcome(s). These steps are common practice in FDA registered trials, but too demanding for under- or unregulated clinics. A recent study (see Murray et al.16 reference for details) has offered a consensus report on the parameters needed to improve cell therapy outcomes for both patients and practitioners using the acronym DOSES: D—Donor, O—Origin tissue, S—Separation Method, E—Exhibited Characteristics, S—Site of Delivery.
Stem Cell Clinics may reference their stem cell lineage as bone marrow stem cells, amniotic membrane stem cells, fat cell and mesenchymal in origin.
Adult/Tissue Stem Cells
Adult stem cells, or “tissue stem cells,” can come from different parts of the adult body. They are specific to a certain kind of tissue in the body: for instance, liver stem cells can regenerate liver tissue, and muscle stem cells can regenerate muscle fibers. But adult stem cells are limited to only becoming more of their specialized tissue—liver stem cells cannot make new muscle fibers, nor can muscle stem cells make new liver tissue.
Cells
The thousands of different cell types that make up our bodies all came from one single “master builder” cell, called a pluripotent stem cell.
Pluripotent stem cells can be thought of as “blank slates,” because of their ability to build any cell type in the body—skin cells, brain cells, muscle cells, etc. Unlike tissue stem cells, pluripotent stem cells are not limited to only becoming more of a certain tissue.
Pluripotent stem cells primarily consist of embryonic stem cells, but the term now also encompasses another type of cells, called “induced pluripotent stem cells.” More on that later.
Induced Pluripotent Stem Cells/iPSCs
Induced pluripotent stem (iPS) cells are pluripotent cells that are derived from adult tissue using new scientific technology. They share characteristics with embryonic stem cells in that they can become any cell type in the body.
Reprogramming stem cells to create iPSCs involves some genetic manipulation, and this may cause some differences that are not present in cells that are already embryonic in nature. It is essential to continue research using all cell types. Because the field of stem cell research is so new, it is critical to explore all avenues of stem cell research, from pluripotent to tissue stem cells.
Although research has been in progress for the past decade or more, we are just beginning to unravel how the embryonic ova differentiates with each cell division. Each division results in an exponential increase in the number of stem cells. With each division, the pluripotential of each cell decreases in an inverse manner. In other words, they will not have the same potential to make certain kinds of tissue (brain, skin, bones, liver, and other organ systems. At maturity and at birth some organs contain a reservoir of stem cells particular to that tissue. Organs with demand for higher cellular division to repopulate the organ such as skin, bone marrow. Skin as an organ continuously requires replacement as the upper layers are shed. The normal time of RBC senescent (age-related) death in adults is approximately 110 to 120 days through a process call erythropoiesis.
Blood Stem cells go on to differentiate as shown in the figure.(s)
Red blood cells are manufactured by a complex loop of protein regulation from the liver and kidneys. The rate is normally 2-3 million RBCs /second when the system is stable, with an equal amount of senescent RBCs being destroyed by eryptosis (scroll down)
This process is balanced by RBC senescence or eryptosis.
Another stem cell line follows a journey much like the progenitor hemocytoblast. The basal layers of skin contain stem cells that begin the process. There are many skin products that claim to stimulate the process using DNA like analog molecules.
The production of a focused stem cell requires an arduous process of trial and error in the lab. Once this is accomplished a Clinical trial will be submitted to the FDA for approval to market the drug. They determine the safety, efficacy and side effects or complication by using the drug in humans.
Early pre-trial studies are done in mice when possible.Biblio:
15 Galipeau, J., Weiss, D. J. & Dominici, M. Response to Nature commentary “Clear up this stem-cell mess”. Cytotherapy 21, 1–2 (2019).
16 Murray, I. R. et al. International expert consensus on a cell therapy communication tool: DOSES. J. Bone Jt. Surg.
* Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement
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