Use of Mesenchymal Cells in Stem Cell Transplants
Dr. Edwin Horwitz
Professor, The Children’s Hospital of Philadelphia and UPenn
I focus my research almost exclusively on the transplantation of marrow cells and mesenchymal stem cells (MSCs) to treat cancer and genetic disorders of childhood. When we do stem cell transplants using MSCs, we’re not doing any pre-conditioning or depletion of the immune system. First of all, part of the role of a conditioning regimen is to get rid of some of the patient’s hematopoietic stem cells (blood making cells) and allow new ones to take over. The MSCs that we infuse do not engraft in any specific place. So there’s no competition and therefore, no need to get rid of anything. Secondly, the other reason to give a conditioning regimen is to suppress the patient’s immune system or perhaps even get rid of their immune system so that there’s no rejection of the donor’s stem cells coming into the patient. Since MSCs do not seem to stimulate an immune response or rejection response in the patient, there’s no need to suppress the immune system.
MSCs go into the body, go wherever they end up, and secrete their magic ingredients and then they circulate in the blood. We have observed that MSCs uniformly seem to migrate to sites of injury, consistent with the concept that MSCs promote the healing process by stimulating a person’s own regenerating mechanisms to heal the tissue.
After we grow the cells and infuse them into the patient, we find that sometimes we get extraordinary responses. Sometimes it’s good, but not extraordinary. What if we could engineer the cells so as to yield an extraordinary response each and every time? That would be a huge step forward, but to do that we need to understand better how they’re working. That’s why it’s important to isolate the MSCs and investigate their secreted molecules, the magic ingredients, which is one of the specific areas that we are researching today.
Perhaps someday we may be able to isolate what the MSCs are secreting and treat patients with this substance (as opposed to treating with MSCs). I’m not sure it will work as it can be difficult to reproduce everything exactly as the MSC does it. But if we understand what that molecule is and how it works, we could potentially select cells, or even engineer cells that do a better job at healing the tissues, to make a better cell therapy with better outcomes for patients.