期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 17, 期 2, 页码 214-225出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2010.08.015
关键词
Hematopoietic cell transplantation; MSC; GVHD; Rejection; Canine model
资金
- National Institutes of Health (NIH), (National Institute of Allergy and Infectious Diseases [NIAID]) [U19AI067770]
- National Cancer Institute [NCI] [P30CA015704]
- National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] [P30DK056465]
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 x 10(6) MSCs/kg/day, 2-5 times/week) or third-party primary MSC (1.0 x 10(6) 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. Biol Blood Marrow Transplant 17: 214-225 (2011) (C) 2011 American Society for Blood and Marrow Transplantation
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据