Bone Marrow Mesenchymal Stem Cells Suppress Lymphocyte Proliferation In Vitro but Fail to Prevent Graft-versus-Host Disease in Mice

TLDR

Mesenchymal stem cells have been reported to exert strong immunosuppressive effects in vitro, suggesting therapeutic potential for T‑cell‑mediated diseases. This study aimed to determine whether MSCs could control graft‑versus‑host disease following allogeneic hematopoietic stem cell transplantation. The authors isolated and expanded MSCs from C57BL/6 and BALB/c mouse bone marrow, confirming their identity by absence of CD45/CD11b, spindle morphology, and multilineage differentiation into osteogenic, chondrogenic, and adipogenic lineages. Although MSCs dose‑dependently inhibited alloantigen‑stimulated T‑cell proliferation in vitro, their addition to bone‑marrow transplants did not reduce GVHD incidence or severity in vivo, likely because they failed to suppress donor T‑cell division in the grafted animals.

Abstract

Abstract Several reports have suggested that mesenchymal stem cells (MSCs) could exert a potent immunosuppressive effect in vitro, and thus may have a therapeutic potential for T cell-dependent pathologies. We aimed to establish whether MSCs could be used to control graft-vs-host disease (GVHD), a major cause of morbidity and mortality after allogeneic hemopoietic stem cell transplantation. From C57BL/6 and BALB/c mouse bone marrow cells, we purified and expanded MSCs characterized by the lack of expression of CD45 and CD11b molecules, their typical spindle-shaped morphology, together with their ability to differentiate into osteogenic, chondrogenic, and adipogenic cells. These MSCs suppressed alloantigen-induced T cell proliferation in vitro in a dose-dependent manner, independently of their MHC haplotype. However, when MSCs were added to a bone marrow transplant at a MSCs:T cells ratio that provided a strong inhibition of the allogeneic responses in vitro, they yielded no clinical benefit on the incidence or severity of GVHD. The absence of clinical effect was not due to MSC rejection because they still could be detected in grafted animals, but rather to an absence of suppressive effect on donor T cell division in vivo. Thus, in these murine models, experimental data do not support a significant immunosuppressive effect of MSCs in vivo for the treatment of GVHD.