Therapeutic Potential of Ovarian Monocyte Progenitor Cells (MPCs) in SLE-Murine Model.

Abstract

We have previously shown that the progeny of resident ovarian stromal progenitor cells is restricted to the production of cells of the monocyte-macrophage lineage. These ovarian monocyte progenitor cells (MPCs) formed hematopoietic colonies on methyl cellulose, and were CD45+, CD11b+, CD11c+, and Ly6-Gr-1. A distinct CD45low population within these cells reacted with CD117 (C-kit) surface marker, suggestive of a primitive hematopoietic progenitor. To determine the therapeutic potential of MPCs, we transplanted 50,000 cells into normal and autoimmune BXSB autoimmune mouse model for SLE. MPCs did not rescue lethally irradiated mice from the consequences of irradiation, and were not engrafted in MHC-mismatched mouse strains. However, murine SLE-like symptoms were improved, and substantial reduction in inflammatory infiltrate was observed in tissue sections from transplanted mice including kidneys, lungs, and spleen. Restructuring of renal glomerural sclerosis was also observed in the transplant recipients. To determine whether glomerular vascular regeneration was directly mediated by donor MPCs, we tested the hypothesis that MPCs co-express markers for endothelial progenitor cells and monocytes. After culture in conditions permissible to endothelial cell differentiation, large percentage of MPCs (73%) expressed endothelial cell marker CD106. When their culture supernatant was applied to a rat aortic ring in matrigel tube forming assay, robust tube formation was observed in the experimental group. However, similar tube formation was also observed in the control well containing 20% FBS, and cultured MPCs failed to produce tube formation in matrigel assay. Interestingly, phenotypic analysis showed that only 52% of MPCs express MHC class I suggesting that these cells may induce less rejection when transplanted in mismatched hosts. These data suggest that vascular tissue repair initiated by MPCs is mediated by anti-inflammatory factors, and not by direct contribution to the reconstruction of glomeular vasculature.