Details

Autor(en) / Beteiligte

• Jitschin, Regina
• Mougiakakos, Dimitrios
• Von Bahr, Lena
• Völkl, Simon
• Moll, Guido
• Ringden, Olle
• Kiessling, Rolf
• Linder, Stig
• Le Blanc, Katarina

Titel

Alterations in the Cellular Immune Compartment of Patients Treated with Third‐Party Mesenchymal Stromal Cells Following Allogeneic Hematopoietic Stem Cell Transplantation

Ist Teil von

• Stem cells (Dayton, Ohio), 2013-08, Vol.31 (8), p.1715-1725

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Cells 2013;31:1715–1725