OBJECTIVE. In vitro proliferative and differentiation potential of mesenchymal stromal cells (MSCs) generated from CD271+ bone marrow mononuclear cells (CD271-MSCs) has been demonstrated in several earlier and recent reports. In the present study we focused, in addition to proliferative and differentiation potential, on in vitro and in vivo immunosuppressive and lymphohematopoietic engraftment-promoting potential of these mesenchymal stromal cells compared to bone marrow-derived mesenchymal stromal cells generated by plastic adherence (PA-MSCs).
MATERIALS AND METHODS. We set up a series of experimental protocols in order to determine the phenotype of bone marrow-derived CD271-MSCs, their clonogenic, proliferative, differentiation and immunosuppressive potential. The potential of CD271-MSCs to improve the engraftment of CD133+ hematopoietic stem cells at co-transplantation was evaluated in immunodeficient NOD/SCID-IL2Rnull mice.
RESULTS. In vitro studies demonstrated that CD271-mesenchymal stromal cells differentiate along adipogenic, osteogenic and chondrogenic lineages (trilineage potential), and significantly inhibit the proliferation of allogeneic T-lymphocytes in mixed lymphocyte reaction assays. Elevated levels of prostaglandin E2, but not nitric monoxide, IL-10 or soluble HLA-G, mediated the majority of this immunosuppressive effect. In vivo studies showed that CD271-mesenchymal stromal cells promoted significantly greater lymphoid engraftment than did PA-MSCs when co-transplanted with CD133+ hematopoietic stem cells at a ratio of 8:1 in immunodeficient NOD/SCID-IL2Rnull mice. They induced a 10.4-fold increase in the number of T cells, a 2.5-fold increase in the number of NK cells, and a 3.6-fold increase in the number of B cells, indicating a major qualitative difference between these two mesenchymal stromal cell populations.
CONCLUSIONS. Our results indicate that CD271 antigen provides a versatile marker for prospective isolation and expansion of MSCs with immunosuppressive and lymphohematopoietic engraftment-promoting properties. The co-transplantation of such cells together with hematopoietic stem cells in patients with hematologic malignancies may prove valuable in the prevention of impaired/delayed T-cell recovery and graft-versus-host disease
