The mechanisms underlying immunomodulatory ability of mesenchymal stromal cells (MSCs) remain unknown. Recently, studies suggested that the immunomodulatory activity of MSCs is largely mediated by paracrine factors. Among which, exosome is considered to play a major role in the communication between MSCs and target tissue. The aim of our study is to investigate the effect of MSCs-derived exosome on peripheral blood mononuclear cells (PBMCs), especially T cells. We find that the MSCs-derived exosome extracted from healthy donors' bone marrow suppressed the secretion of pro-inflammatory factor TNF-α and IL-1β, but increased the concentration of anti-inflammatory factor TGF-β during in vitro culture. In addition, exosome may induce conversion of T helper type 1 (Th1) into T helper type 2 (Th2) cells and reduced potential of T cells to differentiate into interleukin 17-producing effector T cells (Th17). Moreover, the level of regulatory T cells (Treg) and cytotoxic T lymphocyte-associated protein 4 were also increased. These results suggested that MSC-derived exosome possesses the immunomodulatory properties. However, it showed no effects on the proliferation of PBMCs or CD3+ T cells, but increases the apoptosis of them. In addition, indoleamine 2, 3-dioxygenase (IDO) was previously shown to mediate the immunoregulation of MSCs, which was increased in PBMCs co-cultured with MSCs. In our study, IDO showed no significant changes in PBMCs exposed to MSCs-derived exosome. We conclude that exosome and MSCs might differ in their immune-modulating activities and mechanisms.

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Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for severe aplastic anemia (SAA) is mainly limited by the high incidence of graft failure and GvHD. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis in vivo and to display potent immunosuppressive effects to prevent or treat GvHD after HSCT. In a multicenter phase II trial, we developed an approach with co-transplantation of MSCs in patients undergoing haplo-HSCT. Forty-four patients with SAA were included. The conditioning regimen included busulfan, cyclophosphamide and thymoglobulin (ATG). The recipients received cyclosporin A (CsA), mycophenolate mofetil and short-term methotrexate for GvHD prophylaxis. Three out of 44 patients, who died early before hematopoietic engraftment, were not assessed. Evaluable patients (97.6%; 40/41) achieved hematopoietic reconstitution and sustained full donor chimerism. The median time for myeloid engraftment was 12 days (range 8-21 days) and for platelet engraftment was 19 days (range 8-154 days). The incidence was 29.3% for grade II-IV acute GvHD and 14.6% for chronic GvHD. The overall survival was 77.3% with a median 12-month (range 0.9-30.8) follow-up for surviving patients. These data suggest that co-transplantation of MSCs could reduce the risk of graft failure and severe GvHD in haplo-HSCT for SAA.

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