Mesenchymal stem cells attenuate rat graft-versus-host disease

Abstract

Mesenchymal stem cells (MSCs) derived from bone marrow are feasible for the exertion of a powerful immunoregulatory effect and thus shall hold a curative potency in T lymphocyte-dependent pathologies. This current article is intended to describe the method to investigate that MSCs might take advantage of regulation in graft-versus-host disease (GvHD), a major etiology of attack rate and lethality post allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were isolated from Lewis rat bone morrow and cultured for 4 weeks. The purification of enriched conventional MSCs and macrophages was achieved by autoMACS. Using the limiting dilution method, MSCs were cloned and then expanded until more than 6 months. The cultured MSCs showed a typical spindle-shaped morphology and immunophenotypes, lack of CD45 and CD11b/c expression. MSCs are also known for their ability to differentiate into adipocytes. MSCs, like macrophages, exhibit the immunomodulatory propensity to inhibit T lymphocyte proliferation. Following the adoptive transfer, MSCs regulate systemic Lewis to (Lewis × DA) F1 rat GvHD. Meanwhile, the cloned MSCs surprisingly enhanced T cell proliferation in vitro and yielded no clinical benefit in regard to the incidence or severity of GvHD. This is in contradistinction to the immunosuppressive activities of MSCs as conventionally described. Hence, this rat GvHD model treated with MSCs has shown intriguing differences in the regulatory effects of lymphocyte proliferation and GvHD repression between short-term cultured conventional MSCs and cloned MSCs.