Mesenchymal Stem Cells

Originally, Mesenchymal Stem Cells (MSCs) were thought to be the drivers of tissue regeneration. We now know that this is not quite accurate. This comes from the work of Dr. Arnold Caplan. Dr. Caplan is considered one of the Godfathers of stem cell regenerative medicine. What Dr. Caplan taught is the concept that MSCs will dramatically reduce (immuno-modulate) the inflammation in an area affected by an orthopedic disorder. When the inflammation is reduced, repair can take place. The mesenchymal stem cell is a cell that has many tasks but one of its main tasks is to act as an immune modulator. An immune modulator is a cell that reduces the inflammatory response in the body. Perhaps a good analogy to give to a mesenchymal stem cell is to liken it to a Navy Seal. Like a Navy Seal the mesenchymal stem cells are very specialized, parachuted (injected) into a hostile area, and probably will not survive. Their task is to secure the area so that other cells can accomplish their job. They have made the environment much less hostile for other regenerative cells. Mesenchymal stem cells are very plentiful in adipose (fat) tissue but are not as plentiful in bone marrow. When we use fat tissue as a source of Mesenchymal Stem Cells, we do not break the fat tissue down with an enzyme. We feel the best way to utilize the fat is as a free fat graft. One hidden gem in a free fat graft is a special type of cell called a MUSE cell. A Muse Cell does well under stress and more importantly it is considered a pluripotent cell. This means it can form almost any type of tissue. It is most likely found in all free fat grafts.

 


injury response of pericytes

 

The above diagram shows that the mesenchymal stem cells first reduce inflammation (immunomodulation), then they help accomplish repair by a trophic action which involves stimulating other cells to accomplish repair. The trophic effect allows the micro environment around the cell to encourage repair. In summary, people once thought MSCs were drivers of repair, but that is old thinking and needs updating with modern literature results. Are MSCs important? Yes! They are cells supporting hematopoietic stem cells (CD34+) and other stem cells, homing of the stem cells, release of signals, and immunomodulation. CD34+ and MSCs show additive effects when combined. So, having a rich cornucopia of different cells is important for tissue regeneration. Focusing on one cell type never does as well as many cell types, even with growth factors added. A multi cell approach is what nature takes and we do the same.

 

In Orthopedics and other medical specialties we know that some patients with horrible looking X-rays are playing golf and tennis with little pain, yet some patients with minimal changes on X-rays can have significant, disabling symptoms. This can be explained by the fact that certain patients have mesenchymal stem cells that may be eliminating the chronic inflammation observed in osteoarthritis, in rheumatoid arthritis, or with severe focal injuries to skeletal tissues. We also see this from time to time where after stem cell therapy we get little change on x-ray yet the patients become asymptomatic. One concept that we like to stress is that stem cells can accomplish two goals. Sometimes they can form a coating of cells on the joint surfaces and just as important they can change the chemistry of the joint so that the joint is no longer inflamed.