Small Steps Towards a Better Understanding of Mesechymal Stem Cell Therapies

Mesenchymal stem cell therapies are arguably the most robust, practiced, and standardized of the diverse field of stem cell medicine - though this is still something of a low bar to pass. These cell therapies fairly reliably reduce chronic inflammation, and given what is known of the interactions of senescent cells, inflammatory signaling, and dysfunction in regeneration, this might be enough to explain the varied benefits claimed in patients and animal studies, particularly improved healing. Inflammation isn't the whole of the picture, however, and given that signaling by numerous poorly cataloged molecules is involved, developing a better understanding as to exactly why these therapies work at all is a challenging, slow, and ongoing process. In theory, given that better understanding, the cells could be discarded in favor of a cheaper and more reliable therapy involving delivery of signal molecules alone, but that still seems years away at this point.

Therapy with mesenchymal stem cells, the so-called progenitor cells of connective tissue, holds great promise for the regeneration of cartilage tissue but how stem cell therapy contributes to the healing of damaged connective tissue has been unclear. Debate has centered on whether the injected cells promote regeneration or stimulate the body's own cells to proliferate. A new strategy has now enabled researchers to solve the question. The problem was that a marker protein was recognized by the immune system of the recipient as a non-self protein, leading to the rejection of the injected stem cells. The scientists were able to overcome this limitation and show that progenitor cells do not participate directly in cartilage regeneration but serve to "animate" the process.

"To date, it has not been possible to show what an injection of stem cells really does in an animal model. The problem is that you have to track the cells with particular proteins that the immune system of the recipient recognizes as non-endogenous and thus potentially harmful. The resulting rejection of the injected cells has prevented the validation of their mode of action." It was thus only possible to track stem cells in immunodeficient animal models that had no reaction to the proteins due to a genetically reduced immune system. Yet these models could not provide any clues about the mode of action of the stem cells in normal animals. "We therefore worked with a 'lifelike' animal model that is immunocompetent but shows no response to our tracker molecule. This enabled us to show that stem cells have a purely modulating action in the treatment of cartilage damage. Our results contribute to our understanding of stem cell therapy, as they show for the first time that therapy stimulates the body's own cells to promote the regeneration of damaged connective tissue, such as cartilage."

Link: http://www.vetmeduni.ac.at/en/infoservice/presseinformation/press-releases-2017/stem-cells-conduct-cartilage-regeneration-but-are-not-directly-involved/