title: An increase in CD3+CD4+CD25+ regulatory T cells after administration of umbilical cord-derived mesenchymal stem cells during sepsis.
abstract: Sepsis remains an important cause of death worldwide, and vigorous immune responses during sepsis could be beneficial for bacterial clearance but at the price of collateral damage to self tissues. Mesenchymal stem cells (MSCs) have been found to modulate the immune system and attenuate sepsis. In the present study, MSCs derived from bone marrow and umbilical cord were used and compared. With a cecal ligation and puncture (CLP) model, the mechanisms of MSC-mediated immunoregulation during sepsis were studied by determining the changes of circulating inflammation-associated cytokine profiles and peripheral blood mononuclear cells 18 hours after CLP-induced sepsis. In vitro, bone marrow-derived MSCs (BMMSCs) and umbilical cord-derived MSCs (UCMSCs) showed a similar morphology and surface marker expression. UCMSCs had stronger potential for osteogenesis but lower for adipogenesis than BMMSCs. Compared with rats receiving PBS only after CLP, the percentage of circulating CD3+CD4+CD25+ regulatory T (Treg) cells and the ratio of Treg cells/T cells were elevated significantly in rats receiving MSCs. Further experiment regarding Treg cell function demonstrated that the immunosuppressive capacity of Treg cells from rats with CLP-induced sepsis was decreased, but could be restored by administration of MSCs. Compared with rats receiving PBS only after CLP, serum levels of interleukin-6 and tumor necrosis factor-α were significantly lower in rats receiving MSCs after CLP. There were no differences between BMMSCs and UCMSCs. In summary, this work provides the first in vivo evidence that administering BMMSCs or UCMSCs to rats with CLP-induced sepsis could increase circulating CD3+CD4+CD25+ Treg cells and Treg cells/T cells ratio, enhance Treg cell suppressive function, and decrease serum levels of interleukin-6 and tumor necrosis factor-α, suggesting the immunomodulatory association of Treg cells and MSCs during sepsis.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Chao
authors.affiliation: Department of Pediatrics, Taichung Tzuchi Hospital, the Buddhist Medical Foundation, Taichung, Taiwan; Department of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Han-Ping
authors.initials: HP
authors.lastname: Wu
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Hemato-oncology, Children's Hospital, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Kang-Hsi
authors.initials: KH
authors.lastname: Wu
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Departments of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Giien
authors.initials: YG
authors.lastname: Tsai
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Hemato-oncology, Children's Hospital, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan.
authors.forename: Ching-Tien
authors.initials: CT
authors.lastname: Peng
authors.affiliation: School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; Life-Course Epidemiology and Human Development Research Group, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan.
authors.forename: Kuan-Chia
authors.initials: KC
authors.lastname: Lin
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Wan-Ru
authors.initials: WR
authors.lastname: Chao
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Maw-Sheng
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Yun-Ching
authors.initials: YC
authors.lastname: Fu
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D056747:Immunomodulation; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D010006:Osteoblasts / Q000166:cytology / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha