title: Prolongation of Cardiac Allograft Survival by Endometrial Regenerative Cells: Focusing on B-Cell Responses.
abstract: Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive candidate source for emerging stem cell therapies in immunosuppression, but their role in immunoregulation is not fully understood. The present study was designed to investigate their effects, especially on B-cell responses in heart transplantation. In this study, ERCs were noninvasively obtained from menstrual blood. Heart transplantation was performed between C57BL/6 (H-2b) donor mice and BALB/c (H-2d) recipients. B-cell activation and antibody levels were determined using fluorescence-activated cell sorting, enzyme-linked immunosorbent assay and ELISpot. In this study, we demonstrated that ERCs negatively regulated B-cell maturation and activation in vitro without affecting their viability. ERC treatment prolonged cardiac allograft survival in mice, which was correlated with a decrease in IgM and IgG deposition and circulating antidonor antibodies, as well as with reduction in frequencies of antidonor antibody-secreting CD19+B cells. In addition, upon ex vivo stimulation, B cells from ERC-treated heart transplant recipients had impaired proliferation capacity and produced less IgM and IgG antibody. Moreover, ERC treatment of mice receiving ovalbumin (OVA)-aluminum hydroxide vaccine resulted in significant lower numbers of anti-OVA IgG antibody-secreting splenic B cells and lower anti-OVA antibody titres. Our results indicate that therapeutic effects of ERCs may be attributed at least in part by their B-cell suppression and humoral response inhibition, suggesting the potential use of ERCs for attenuating antibody-mediated allograft rejection. Stem Cells Translational Medicine 2017;6:778-787.
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.|Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Bai
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Hongqiu
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of General Surgery, Affiliated Hospital of Weifang Medical University, Shandong, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Caigan
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.|Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D064591:Allografts / Q000502:physiology*; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004717:Endometrium / Q000166:cytology*; D005260:Female; D006085:Graft Survival; D016027:Heart Transplantation; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000378:metabolism; D012038:Regeneration; D014611:Vaccination
chemical_list: D000906:Antibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D010047:Ovalbumin
keywords: Antibody-mediated rejection; B lymphocytes; Endometrial regenerative cells; Heart transplantation; Immunosuppression; Mice