by Daniel F. Royal, DO, HMD, JD
When I lecture on the subject of “stem cells” the first thing I like to do is define the term. The reason for this is there seems to be confusion on this subject of stem cells for both patients and physicians alike. For example, a “stem cell” is understood to be a cell that has the ability to differentiate into all three germ cell layers (incl., ectoderm, endoderm, and mesoderm). This characteristic of stem cells is referred to as “pluripotency.” In addition, stem cells are known to divide indefinitely. This is because the proverbial “biological clock” doesn’t begin ticking until the process of differentiation has been initiated.
On the other hand, precursor cells (a.k.a. “progenitor cells”) have a limited life span known as “Hayflick’s Limit.” Hayflick’s Limit refers to the fact that all precursor cells demonstrate a finite life span of 50 to 70 population doublings before programmed cell death occurs. Actual stem cells such as “germ-layer lineage stem cells” and “pluripotent stem cells” exhibit extended capabilities for self-renewal, far surpassing the limited life span of precursor cells (see “Adult reserve stem cells and their potential for tissue engineering,” Young et al., Cell Biochem Biophys. 2004;40(1):1-80).
Despite the fact that our human biological clock begins at birth, it is generally known that “adult stem cells” can still be found in all tissues of the human body. These adult stem cells comprise about 5% of human tissues (incl., totipotent stem cells, pluripotent stem cells, and germ-layer lineage stem cells). Another 45% of our cells are precursor cells that are already partially differentiated and are the immediate precursors for differentiated cells. Differentiated cells comprise the remaining 50% of our cells (e.g., chondroblasts for cartilage, osteoblasts for bone, adipoblasts for fat, etc.)
Germ-layer lineage stem cells can form a wider range of cell types than precursor cells. An individual germ-layer lineage stem cell can form all cells types within its respective germ-layer lineage (i.e., ectoderm, mesoderm, or endoderm). Pluripotent stem cells can form an even wider range of cell types than a single germ-layer lineage stem cell in that a single pluripotent stem cell can form cells belonging to all three germ layer lineages. However, precursor cell tissue sources can only differentiate into specific cell types within one of the mesoderm, endoderm, or ectoderm layers but not all of them.
For example, the primary cells harvested from bone marrow and fat tissue are “mesenchymal precursor cells.” These cells are often identified in the laboratory with as containing the “CD34+.” CD34+ is a marker for hematopoietic and mesenchymal cells, which are often referred to as “mesenchymal stem cells.” However, mesenchymal cells are not stem cells. Rather, they are precursor cells that can only differentiate into mesoderm tissues but not endoderm tissues (incl., liver, lung, gut, pancreas) or ectoderm tissues (incl., skin and nervous system). Instead, mesenchymal cells will only differentiate into cardiovascular and joint tissues (incl., muscle, fat, bone, cartilage, connective tissue, endothelial cells, blood cells, etc.).
The concern arises when a physician (or clinic) advertises that he uses “stem cells” when they are, in fact, mesenchymal cells harvested from either bone marrow or fat tissue. Such advertising is misleading at best. However, offering to use such cells to regenerate organs or tissues that originated from endodermal or ectodermal germ cell layers is a potential fraud, which is generally defined as the “intentional perversion of truth in order to induce another to part with something of value.”
Now, suppose a physician tells a patient that the mesenchymal cells extracted from his bone marrow or fat tissue will “regenerate your liver from cirrhosis” or that “your lungs will regenerate 90 percent after 6 months.” This would be considered a false statement or “perversion of truth.” Now imagine the physician charges $25,000 for the “stem cell procedure.” The prior false statement is used to “induce another to part with something of value” which, in this case, is $25,000. Often, when the procedure fails to work as promised, and the patient’s condition worsens, the physician tells such patients they must repeat the procedure for another $25,000.
Here, the physician is either ignorant of the limitations of mesenchymal cells or he intentionally deceived the patient in order to make a profit. Regardless, based upon the foregoing facts, the physician has now set himself up for a malpractice action that he will not be able to defend. Worst of all, in addition to the false statement, the physician made promises or guarantees to the patient. This is something we simply do not do in medicine because we cannot predict how a patient is going to react to anything. Thus, when the physician’s promise goes unfilled it can only end badly for the physician (see Hawkins v McGee, 84 N.H. 114, 146 A. 641 (N.H. 1929)). Therefore, in order for regenerative medicine physicians to maximize success and minimize failure for their patients, they must fully understand the difference between mesenchymal cells and pluripotent cells and prescribe them appropriately for those conditions for which such cells have the potential of improving.
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