Bone marrow stromal cell transplants prevent experimental enterocolitis and require host CD11b+ splenocytes

Abstract

Background & aims: Bone marrow stromal cells (MSCs) are being evaluated as a cellular therapeutic for immune-mediated diseases. We investigated the effects of MSCs in mice with chemically induced colitis and determined the effects of CD11b(+) cells based on the hypothesis that MSCs increase numbers of regulatory T cells.

Methods: Colitis was induced in mice using trinitrobenzene sulfonic acid; symptoms were monitored as a function of MSC delivery. An immunomodulatory response was determined by measuring numbers of regulatory T cells in mesenteric lymph nodes. In vitro cocultures were used to assess the interaction of MSCs with regulatory T cells and CD11b(+) cells; findings were supported using near-infrared tracking of MSCs in vivo. We chemically and surgically depleted splenic CD11b(+) cells before colitis was induced with trinitrobenzene sulfonic acid to monitor the effects of MSCs. We adoptively transferred CD11b(+) cells that were cocultured with MSCs into mice with colitis.

Results: Intravenous grafts of MSCs prevented colitis and increased survival times of mice. Numbers of Foxp3(+) regulatory T cells increased in mesenteric lymph nodes in mice given MSCs. MSCs increased the numbers of Foxp3(+) splenocytes in a CD11b(+) cell-dependent manner. Transplanted MSCs colocalized near splenic CD11b(+) cells in vivo. Loss of CD11b(+) cells eliminated the therapeutic effect of MSCs. MSCs increased the anticolitis effects of CD11b(+) cells in mice.

Conclusions: MSC transplants, delivered by specific parameters, reduce colitis in mice. Interactions between MSC and CD11b(+) regulatory T cells might be used to develop potency assays for MSCs, to identify nonresponders to MSC therapy, and to create new cell grafts that are composed of CD11b(+) cells preconditioned by MSCs.