title: Adoptive Transfer of Treg Cells Combined with Mesenchymal Stem Cells Facilitates Repopulation of Endogenous Treg Cells in a Murine Acute GVHD Model.
abstract: Therapeutic effects of combined cell therapy with mesenchymal stem cells (MSCs) and regulatory T cells (Treg cells) have recently been studied in acute graft-versus-host-disease (aGVHD) models. However, the underlying, seemingly synergistic mechanism behind combined cell therapy has not been determined. We investigated the origin of Foxp3+ Treg cells and interleukin 17 (IL-17+) cells in recipients following allogeneic bone marrow transplantation (allo-BMT) to identify the immunological effects of combined cell therapy. Treg cells were generated from eGFP-expressing C57BL/6 mice (Tregegfp cells) to distinguish the transferred Treg cells; recipients were then examined at different time points after BMT. Systemic infusion of MSCs and Treg cells improved survival and GVHD scores, effectively downregulating pro-inflammatory Th×and Th17 cells. These therapeutic effects of combined cell therapy resulted in an increased Foxp3+ Treg cell population. Compared to single cell therapy, adoptively transferred Tregegfp cells only showed prolonged survival in the combined cell therapy group on day 21 after allogeneic BMT. In addition, Foxp3+ Treg cells, generated endogenously from recipients, significantly increased. Significantly higher levels of Tregegfp cells were also detected in aGVHD target organs in the combined cell therapy group compared to the Treg cells group. Thus, our data indicate that MSCs may induce the long-term survival of transferred Treg cells, particularly in aGVHD target organs, and may increase the repopulation of endogenous Treg cells in recipients after BMT. Together, these results support the potential of combined cell therapy using MSCs and Treg cells for preventing aGVHD.
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Eun-Sol
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Lim
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Keon-Il
authors.initials: KI
authors.lastname: Im
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Nayoun
authors.initials: N
authors.lastname: Kim
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Nam
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, Korea; Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Jeon
authors.affiliation: Institute for Translational Research and Molecular Imaging, The Catholic University of Korea College of Medicine, Seoul, Korea; Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic Disease, The Catholic University of Korea College of Medicine, Seoul, Korea; Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.
authors.forename: Seok-Goo
authors.initials: SG
authors.lastname: Cho
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000637:transplantation*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D049452:Green Fluorescent Proteins