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- Title
Alterations in the Cellular Immune Compartment of Patients Treated with Third-Party Mesenchymal Stromal Cells Following Allogeneic Hematopoietic Stem Cell Transplantation.
- Authors
Jitschin, Regina; Mougiakakos, Dimitrios; Von Bahr, Lena; Völkl, Simon; Moll, Guido; Ringden, Olle; Kiessling, Rolf; Linder, Stig; Le Blanc, Katarina
- Abstract
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. S TEM C ells 2013;31:1715-1725
- Subjects
STROMAL cells; GRAFT versus host disease; IMMUNE system; PLACEBOS; T cells; STEM cells
- Publication
Stem Cells, 2013, Vol 31, Issue 8, p1715
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.1386