Mesenchymal Stem Cell in Mice Uterine and Its Therapeutic Effect on Osteoporosis.

Abstract

Osteoporosis is a silent disease caused by low bone mineral density and is complicated by fractures. This study was designed to examine the differentiation of uterine stem cell-derived osteoprogenitor cells (UOPCs) both in vitro and in vivo, assessing their effectiveness in treating osteoporosis. CD271⁺/CD45^- UOPCs were isolated from the endometrial tissue of inbred Balb/c mice through magnetic activated cell sorting. Stem cell differentiation assays were used for CD271⁺/CD45^- UOPCs in vitro. In vivo, the UOPCs were implanted into mouse osteoporosis models through tail-vein injection for 8 weeks. Osteogenic differentiation was examined by X-rays and computed tomography (CT) scans. Enhanced green fluorescent protein (EGFP)-labeled UOPCs, obtained from C57BL/6-Tg (ACTb-EGFP) 1Osb/J mice, were used to assess cell survival in the osteoporosis model. The levels of osteogenic markers were assessed by enzyme-linked immunosorbent assay. In vitro, UOPCs were able to form into typical spheres and various differentiations. In vivo, implantation of UOPCs into osteoporosis model significantly increased bone mineral densities and bone microstructure parameters. The levels of a biochemical marker of bone metabolism, Semaphorin-3A, increased significantly. However, levels of receptor activator of nuclear factor kappa-B ligand decreased. Immunofluorescence staining of osteoporosis mice injected with green fluorescent protein+ UOPCs showed their survival for up to 7 days. In conclusion, stem cells with osteogenic differentiation potential can be isolated from uterine or endometrial tissue. These UOPCs can stably proliferate and differentiate in vitro or in vivo, which can inhibit bone resorption and osteoclast marker expression. In vivo, UOPCs significantly improved reduction in bone density caused by reduced estrogen levels. Such cell transplantation approach is potentially useful in the treatment of osteoporosis.