Abstract
Mesenchymal stromal cells (MSCs) have been shown to have immunosuppressive effects in vitro. To test the hypothesis that these effects can be harnessed to prevent graft-versus-host disease (GVHD) and graft rejection after hematopoietic cell transplantation (HCT), we administered a combination of 3 different immortalized marrow-derived MSC lines (15-30 × 106 MSCs/kg/day, 2-5 times/week) or third-party primary MSC (1.0 × 106 MSCs/kg/day, 3 times/week) to canine recipients (n = 15) of dog leukocyte antigen-haploidentical marrow grafts prepared with 9.2 Gy of total body irradiation. Additional pharmacological immunosuppression was not given after HCT. Before their in vivo use, the MSC products were shown to suppress alloantigen-induced T cell proliferation in a dose-dependent, major histocompatibility complex-unrestricted, and cell contact-independent fashion in vitro. Among 14 evaluable dogs, 7 (50%) rejected their grafts and 7 engrafted, with ensuing rapidly fatal acute GVHD (50%). These observations were not statistically different from outcomes obtained with historical controls (n = 11) not given MSC infusions (P=.69). Thus, survival curves for MSC-treated dogs and controls were virtually superimposable (median survival, 18 vs 15 days, respectively). Finally, outcomes of dogs given primary MSCs (n = 3) did not appear to be different from those given clonal MSCs (n = 12). In conclusion, our data fail to demonstrate MSC-mediated protection against GVHD and allograft rejection in this model.
Original language | English (US) |
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Pages (from-to) | 214-225 |
Number of pages | 12 |
Journal | Biology of Blood and Marrow Transplantation |
Volume | 17 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2011 |
Funding
This project was supported by National Institutes of Health (NIH) Grants U19AI067770 ( National Institute of Allergy and Infectious Diseases [NIAID] ), P30CA015704 ( National Cancer Institute [NCI] ), and P30DK056465 ( National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, NIAID, NCI, or NIDDK.
Keywords
- Canine model
- Hematopoietic cell transplantation
- MSC, GVHD
- Rejection
ASJC Scopus subject areas
- Transplantation
- Hematology