title: Immunological characteristics of human umbilical cord mesenchymal stem cells and the therapeutic effects of their transplantion on hyperglycemia in diabetic rats.
abstract: Islet transplantation involves the transplantation of pancreatic islets from the pancreas of a donor to another individual. It has proven to be an effective method for the treatment of type 1 diabetes. However, islet transplantation is hampered by immune rejection, as well as the shortage of donor islets. Human umbilical cord Wharton's jelly-derived mesenchymal stem cells (HUMSCs) are an ideal cell source for use in transplantation due to their biological characteristics and their use does not provoke any ethical issues. In this study, we investigated the immunological characteristics of HUMSCs and their effects on lymphocyte proliferation and the secretion of interferon (IFN)-γ, and explored whether direct cell-to-cell interactions and soluble factors, such as IFN-γ were important for balancing HUMSC-mediated immune regulation. We transplanted HUMSCs into diabetic rats to investigate whether these cells can colonize in vivo and differentiate into pancreatic β-cells, and whether the hyperglycemia of diabetic rats can be improved by transplantation. Our results revealed that HUMSCs did not stimulate the proliferation of lymphocytes and did not induce allogeneic or xenogeneic immune cell responses. qRT-PCR demonstrated that the HUMSCs produced an immunosuppressive isoform of human leukocyte antigen (HLA-I) and did not express HLA-DR. Flow cytometry revealed that the HUMSCs did not express immune response-related surface antigens such as, CD40, CD40L, CD80 and CD86. IFN-γ secretion by human peripheral blood lymphocytes was reduced when the cells were co-cultured with HUMSCs. These results suggest that HUMSCs are tolerated by the host in an allogeneic transplant. We transplanted HUMSCs into diabetic rats, and the cells survived in the liver and pancreas. Hyperglycemia of the diabetic rats was improved and the destruction of pancreatic cells was partly repaired by HUMSC transplantation. Hyperglycemic improvement may be related to the immunomodulatory effects of HUMSCs. However, the exact mechanisms involved remain to be further clarified.
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Hongwu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ni
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Weizhao
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Limin
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Shenzhen Pingshan Women's And Children's Hospital, Shenzhen, Guangdong 518118, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Min
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Lai
authors.affiliation: Transformation Medical Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Yunbin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Guyu
authors.initials: G
authors.lastname: Ho
authors.affiliation: Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China.
authors.forename: Lian
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D015234:HLA-A Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology / Q000628:therapy*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D015703:Antigens, CD; D015234:HLA-A Antigens; C037164:HLA-A28 antigen; D006684:HLA-DR Antigens; D007371:Interferon-gamma