Mesenchymal Stem Cell Therapy for Active Systemic Lupus Erythematosus

There is a soaring interest in MSCs as therapeutics in a variety of immune mediated diseases. Lupus would appear to be a prime candidate for MSC therapy. Uncontrolled trials using freshly derived metabolically active MSCs from healty donors suggest significant clinical benefit. There has yet to be a controlled clinical trial to truly test their efficacy. Mass produced industry provided cells do not appear to be effective as evidenced by the failure of the OSIRIS trials compared to successful European trials using fresh cells. We postulate this difference is due to the massive expansion of the cells with multiple passages of the MSCs commercially produced (10,000 doses/cell line). It is clear that these cells enter senescence after 5-7 passages and lose their immune suppressive properties. The cells were not tested for their immunosuppressive properties and it is clear that not all cells are equally effective. Interferon induced IDO expression and blocking T cell proliferation are possible screens for effectiveness. Finally commercial cells are frozen in DMSO, thawed for one hour and infused. Dr. Galipeau has presented data indicating that the thawing results in a heat shock reaction that renders the cells metabolically inactive. The cells can be reactivated by culturing them for 24-48 hours. Our data indicate, as well as the limited trials of autologous MSCs in lupus, that lupus MSCs are not effective in treating lupus. Thus allogeneic cells are proposed as the source. This may lead to an allogenic response in 30% of patients that would limit repeated infusions. We will also assess for allogenic responses after infusions. In summary, preliminary studies are very promising that MSC infusions offer a relatively safe highly effective treatment for lupus. A controlled clinical trial is essential and timely for determining the impact of this cellular therapy in lupus.