Mesenchymal Stem Cells From Patients With Secondary Progressive Multiple Sclerosis Show Deficient Immunomodulatory Activity Towards Homologous Immune Cells

Objective: To compare the immunomodulatory activity of mesenchymal stem cells from patients with MS and healthy volunteers against autologous immune cells Background: Mesenchymal Stem Cells (MSCs) have been considered promising for the treatment of progressive MS due to their immunomodulatory capacity and potential for providing neuroprotection and repair. Previous studies have shown differential ability of MSC to regulate Th17 and Th1 cells, but few if any studies have compared directly immunomodulatory effects of MSC from MS patients and healthy volunteers towards autologous immune cells such as peripheral blood mononuclear cells (PBMC). MSC effects on T cells expressing GM-CSF are not known. Design/Methods: PBMC from 5 SPMS patients and 6 healthy controls (HC) were stimulated with anti-CD3/CD28 in monoculture or coculture with autologous bone marrow MSC (u003e95% MSC phenotype panel positive, passage 5 or 6) for 72h and 5h restimulation with PMA/ionomycin, followed by intracellular staining for IL-17, IFN-γ, and GM-CSF. Supernatants of MSC prior to co-culture were tested for a panel of cytokines and chemokines using a multiplex array (Merck Millipore). Results: MSC from MS patients produced less IL-10 than those from HC. MSC from HC reduced the proportion of autologous T cells expressing IL-17 (here named Th17) , whereas those from MS patients increased autologous Th17 cells. Conclusions: MSC from SPMS patients have deficient immunomodulatory ability towards immune cells from the same patients, compared to MSC from HC in interaction with autologous immune cells. This is reflected by opposite efefcts on Th17 from MS vs HC. This may be related to a deficient production of IL-10. Although MSC trials are feasible, immunological monitoring is necessary. Study Supported by: Multiple Sclerosis Society of Great Britain and Northern Ireland. Disclosure: Dr. Constantinescu has nothing to disclose. Dr. Frakich has nothing to disclose. Dr. Thevathas has nothing to disclose. Dr. Tanasescu has nothing to disclose. Dr. Gran has nothing to disclose. Dr. Spendlove has nothing to disclose. Dr. Chang has nothing to disclose. Dr. Jones has nothing to disclose.