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

Biju Parekkadan, Rabi Upadhyay, Joshua Dunham, Yoshiko Iwamoto, Emiko Mizoguchi, Atsushi Mizoguchi, Ralph Weissleder, Martin L. Yarmush

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)966-975.e4
JournalGastroenterology
Volume140
Issue number3
DOIs
StatePublished - Mar 2011

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Keywords

  • Crohn's Disease
  • Imaging
  • Mesenchymal Stem Cells
  • Monocyte

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