Rheumatoid Arthritis Model Treated by Mesenchymal Stem Cells

Here is my opinion on why we are not using stem cells more often as a practical medicament as opposed to just doing research for the sake of research: 

Stem cell therapeutics can be seen as an extension of complementary medicine in that its main focus is using the body’s own innate healing powers therapeutically: the same overarching principle that guides naturopaths, chiropractors, and wholistic health practitioners.  On the other hand, the scientific field of stem cell research (and funding) is largely controlled by sophisticated molecular and cell biologists whose overarching desire is minimalistic deconstruction of biological processes so as to understand events at a highly defined level.  Both of these approaches are highly commendable and need to be supported…yet both of these approaches are often seen as arch-enemies, a fact that is slowing down medical progress. 

One particular manifestation of this rivalry between complementary medicine and the concept of using stem cells as a healing factor versus basic researchers who are studying the molecular intricacies of stem cells can be seen in the heated debated between embryonic and adult stem cells. 

Adult stem cells are part of the body’s natural healing process.  When a whole limb is cut from a salamander, an active stem cell compartment allows for its regeneration.  In humans regenerative activity is not as potent but still exists.  For example, stroke patients in which high numbers of bone marrow stem cells entering circulation and home towards the brain have a better outcome than patients in which a lower number of stem cells are detected.  Other studies have demonstrated that after a heart attack stem cells enter the damaged muscle and contribute to repair.  Perhaps the most potent example of stem cell activity is in the liver, where even after 75% reduction in mass the liver regenerates.  Thus adult stem cells are part of the body’s repair system. 

The field of adult stem cells was born with the discovery of a cell population capable of self renewing and making other differentiated cells, this cell was the bone marrow hematopoietic (blood making) stem cell.  Application of this finding to the field of hematology allowed for development of bone marrow transplantation, a procedure that has saved thousands of lives.  Discoveries in the late 1990s demonstrated that bone marrow cells not only make blood but also have other activities such as ability to become different tissues including cardiac muscle, neurons, and liver.  Stunning observations that female recipients of male bone marrow transplants would have Y-chromosome positive cardiac muscle cells further supported the idea that the body has a stem cell pool that is involved not only in repair of damaged tissue but also maintenance of tissue quality by continual replenishment of old tissue by tissue made from the body’s own stem cells. 

Thus the goal of adult stem cell therapy is to enhance the body’s own healing activity by either: a) taking stem cells from one compartment of the body and placing them in another compartment where they are needed, with or without expansion in between; or b) giving the patient stem cells that come from an unrelated source that have the property of not being rejected by the incompatible recipient.

Studies of mouse embryonic stem cells have allowed the creation of genetically manipulated animals, such as knock-outs and transgenics, which have been instrumental in elucidating the in vivo functions of genes.  Human ES research came to the forefront of people’s minds with Jamie Thomas’s publication describing totipotent (they can become all tissues), expandable, and stable cells.  For a variety of reasons embryonic stem cell research has largely overshadowed adult stem cell research in the public consciousness.  99% of people assume “stem cells” is the same as “embryonic stem cells”.  The few that have heard of “adult stem cells” believe them to be a “weaker version” of embryonic stem cells, or cells that can only become blood cells.  This lack of understanding of the difference and therapeutic applicability of between embryonic and adult stem cells has exacerbated the rift between embryonic and adult stem cell efforts.

There is no question that embryonic stem cells are much more “plastic” in ability to become other tissues as compared to adult stem cells.  At face value this would indicate superiority of the embryonic stem cell.  Unfortunately it is this advantage that is also one of the greatest disadvantages for embryonic stem cells.  During development from the fertilized egg until adulthood, the body undergoes a series of very highly orchestrated changes in which the initial one cell becomes daughter cells, and those daughter cells become grand-daughter cells, and so on.  With each step of division some cells “are told” by chemical signals to become skin cells, others to become liver cells, others to become brain cells, until the body has its repertoire of XX unique cell types.  This process is called differentiation.  When contemplating therapy with embryonic stem cells, for example of spinal cord injury, the embryonic stem cells are needed to become new nerves.  New adult nerves.  The steps of going from an embryonic stem cell into an adult nerve takes years and decades if it was occurring naturally.  With embryonic stem cell therapy we are asking the cells to become nerves in a matter of days.  This requirement for acceleration of maturation and skipping some of the normal biological processes makes therapy with ES generated cells artificial.  In other words we are asking the cells to do something that is unnatural.  Unfortunately the problem is not limited to the possibility that the ES derived cells will not work because of this “fast forward” differentiation.  The problem is bigger in that the ES cell may become cancerous. 

Cancer occurs when cells of the body that are differentiated start to ignore the regulatory signals of the body and go out on their own.  Because of mutations that activate genes that normally are silent in the adult, the cancer cell mimics an undifferentiated, or even an embryonic-like cell.  We know this not only from the molecular level, since many genes found in embryonic stem cells are found in cancer cells, but also at the visual level in that the more aggressive .tumor is the more undifferentiated it looks.  During normal development the cells Because embryonic stem cells have a place in the body to grow a specific way, usually cancer doesn’t occur in the natural situation of development.  Unfortunately when embryonic stem cells are placed in the context of an adult body, they form aggressive tumors known as teratomas.  In some cases even embryonic stem cells that have been chemically differentiated in vitro can also become tumors.

Along the lines of arthritis, you may want to look at the work of www.vet-stem.com who have successfully treated thousands of animals in the US with their own fat derived stem cells.