title: Alterations in the cellular immune compartment of patients treated with third-party mesenchymal stromal cells following allogeneic hematopoietic stem cell transplantation.
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.
authors.affiliation: Department of Medicine, Karolinska Institutet, Hematology Center, Karolinska University Hospital, Stockholm, Sweden. regina.jitschin@ki.se.
authors.forename: Regina
authors.initials: R
authors.lastname: Jitschin
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mougiakakos
authors.forename: Lena
authors.initials: L
authors.lastname: Von Bahr
authors.forename: Simon
authors.initials: S
authors.lastname: Völkl
authors.forename: Guido
authors.initials: G
authors.lastname: Moll
authors.forename: Olle
authors.initials: O
authors.lastname: Ringden
authors.forename: Rolf
authors.initials: R
authors.lastname: Kiessling
authors.forename: Stig
authors.initials: S
authors.lastname: Linder
authors.forename: Katarina
authors.initials: K
authors.lastname: Le Blanc
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology*; D008875:Middle Aged; D014184:Transplantation, Homologous
keywords: Hematopoietic stem cell transplantation; Immune reconstitution; Immunotherapy; Mesenchymal stem cells