期刊
STEM CELLS
卷 31, 期 8, 页码 1715-1725出版社
WILEY
DOI: 10.1002/stem.1386
关键词
Mesenchymal stem cells; Immunotherapy; Hematopoietic stem cell transplantation; Immune reconstitution
资金
- Cancer Society of Stockholm
- Children's Cancer Foundation
- Karolinska Institutet
- Stockholm City Council
- Swedish Cancer Society
- Swedish Research Council
- Swedish Society of Medicine
- Tobias Foundation
- VINNOVA
- Max-Eder research grant of the Deutsche Krebshilfe
- IZKF Erlangen grant
Adoptive transfer of third-party mesenchymal stromal cells (MSCs) has emerged as a promising tool for the treatment of steroid-refractory graft-versus-host disease (GVHD). Despite numerous in vitro studies and preclinical models, little is known about their effects on the patients' immune system. We assessed immune alterations in the T-cell, B-cell, natural killer cell, dendritic cell, and monocytic compartments of steroid-refractory GVHD patients 30, 90, and 180 days after MSC (n = 6) or placebo (n = 5) infusion, respectively. Infused MSCs were bioactive as suggested by the significant reduction in epithelial cell death, which represents a biomarker for acute GVHD. There were several indications that MSCs shift the patients' immune system toward a more tolerogenic profile. Most importantly, infusion of MSCs was associated with increased levels of regulatory (forkhead box P3 (FOXP3)(+) and interleukin (IL)-10(+)) T-cells, reduced pro-inflammatory IL-17(+) T(Th17)-cells, and skewing toward type-2 T-helper cell responses. Furthermore, IL-2, which has been recently shown to exert a positive immune modulating effect in GVHD patients, was higher in the MSC patients at all evaluated time points during 6 months after MSC-infusion. Overall, our findings will contribute to the refinement of monitoring tools, for assessing MSC treatment-efficacy and increase our understanding regarding the MSCs' in vivo effects. STEM Cells2013;31:1715-1725
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