Interleukin-35 mediates hepatoprotective effect of PMSC-11 personalized mesenchymal stem cells 4787

Abstract Description Mesenchymal stem cells (MSC) have been demonstrated to suppress various aspects of liver failure through immunologic and regenerative mechanisms. PMSC-11 is an MSC-based therapeutic developed from retro-differentiated peripheral blood that is under preclinical development for treatment of liver failure. Materials and Methods PMSC-11 was assessed in the carbon tetrachloride and acetaminophen induced liver failure models. Enzyme levels, cytokine production and alternations of cellular phenotypes were assayed. Adoptive transfer of immune populations was performed into naïve mice. Antibody mediated cytokine neutralization was performed. Results and Discussion: PMSC-11 was superior to saline control, as well as bone marrow, adipose, and umbilical cord derived MSC at preventing liver failure. Therapeutic response was associated with increased numbers of putative iTR35 cells, which were capable of transferring production from liver failure to naïve mice. The therapeutic effects were abrogated by antibody mediated neutralization of IL-35. These results provide possible mechanistic basis for PMSC-11 mediated production against liver failure. Funding Sources Supported by Immorta Bio Inc Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)