Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease

Publication date: Available online 1 February 2019Source: Stem Cell ResearchAuthor(s): E. Ilker Ozay, Jyothi Vijayaraghavan, Gabriela Gonzalez-Perez, Sudarvili Shanthalingam, Heather L. Sherman, Daniel T. Garrigan, Karthik Chandiran, Joe A. Torres, Barbara A. Osborne, Gregory N. Tew, Igor I. Slukvin, Ross A. Macdonald, Kilian Kelly, Lisa M. MinterAbstractThe immune-mediated tissue destruction of graft-vs-host disease (GvHD) remains a major barrier to greater use of hematopoietic stem cell transplantation (HSCT). Mesenchymal stem cells (MSCs) have intrinsic immunosuppressive qualities and are being actively investigated as a therapeutic strategy for treating GvHD. We characterized Cymerus™ MSCs, which are derived from adult, induced pluripotent stem cells (iPSCs), and show they display surface markers and tri-lineage differentiation consistent with MSCs isolated from bone marrow (BM). Administering iPSC-MSCs altered phosphorylation and cellular localization of the T cell-specific kinase, Protein Kinase C theta (PKCθ), attenuated disease severity, and prolonged survival in a humanized mouse model of GvHD. Finally, we evaluated a constellation of pro-inflammatory molecules on circulating PBMCs that correlated closely with disease progression and which may serve as biomarkers to monitor therapeutic response. Altogether, our data suggest Cymerus iPSC-MSCs offer the potential for an off-the-shelf, cell-based therapy to treat GvHD.Graphical abstract
Source: Stem Cell Research - Category: Stem Cells Source Type: research