A new study, appearing in Cell Stem Cell and led by researchers at USC, outlines the specifics of how autoimmune disorders can be controlled by infusions of mesenchymal stem cells (MSC).
Highly versatile MSC originate from the mesoderm, or middle layer of tissue, in a developing embryo. MSC can be isolated from several kinds of human tissue, including bone marrow and the umbilical cord.
Principal investigator Songtao Shi, professor at the Ostrow School of Dentistry of USC’s Center for Craniofacial Molecular Biology, said recent studies have shown the benefits of administering MSC to patients with immune-related disorders, such as graft versus host disease, systemic lupus erythematosus and rheumatoid arthritis.
These studies showed that infusions of MSC appeared to quell the production and function of overactive immune cells, including T- and B-lymphocytes. However, the specific mechanism behind how MSC get the immune cells under control hasn’t been fully understood.
“MSC-Induced Immunoregulation Involves FAS-Ligand-/FAS-Mediated T Cell Apoptosis” examined how infused MSCs target and defeat overactive immune cells. Looking at the effects of MSC infusion in mice with systemic sclerosis (SS)-like immune disorders, Shi and his colleagues discovered that a specific cellular mechanism known as the FAS/FAS-ligand pathway was the key to the remarkable immune system benefits.
Specifically, in mice with SS-like disorders, infusions of MSC caused T-lymphocyte death with FASL/FAS signaling and lessened symptoms of the immune disorder. However, MSC deficient in FAS-ligand failed to treat immune disorders in SS-afflicted mice.
With the hopeful results of the animal model study in mind, Shi’s colleagues in China performed a pilot study with patients suffering from SS. Infusions of MSCs provided similar clinical benefits to patients, and experimental analysis revealed that the FASL/FAS pathway also was at work in humans with SS.
The identification of the cellular workings responsible for the success of the stem cell treatments eventually may help doctors find optimal cell-based treatment for some immune diseases, Shi said.
The National Institute of Dental and Craniofacial Research and the California Institute for Regenerative Medicine supported basic research portions of the study. Clinical studies were supported by a grant from the China Major International (Regional) Joint Research Project.