PMID- 24297321 OWN - NLM STAT- MEDLINE DCOM- 20140918 LR - 20211021 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 33 IP - 2 DP - 2014 Feb TI - Immunological characteristics of human umbilical cord mesenchymal stem cells and the therapeutic effects of their transplantion on hyperglycemia in diabetic rats. PG - 263-70 LID - 10.3892/ijmm.2013.1572 [doi] AB - 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)-gamma, and explored whether direct cell-to-cell interactions and soluble factors, such as IFN-gamma 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 beta-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-gamma 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. FAU - Wang, Hongwu AU - Wang H AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Qiu, Xiaoyan AU - Qiu X AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Ni, Ping AU - Ni P AD - Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Qiu, Xuerong AU - Qiu X AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Lin, Xiaobo AU - Lin X AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Wu, Weizhao AU - Wu W AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Xie, Lichun AU - Xie L AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Lin, Limin AU - Lin L AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Min, Juan AU - Min J AD - Department of Obstetrics and Gynecology, Shenzhen Pingshan Women's And Children's Hospital, Shenzhen, Guangdong 518118, P.R. China. FAU - Lai, Xiulan AU - Lai X AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Chen, Yunbin AU - Chen Y AD - Transformation Medical Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Ho, Guyu AU - Ho G AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. FAU - Ma, Lian AU - Ma L AD - Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131128 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Antigens, CD) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A28 antigen) RN - 0 (HLA-DR Antigens) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Antigens, CD/metabolism MH - Cell Communication MH - Cell Proliferation MH - Cells, Cultured MH - Coculture Techniques MH - Disease Models, Animal MH - HLA-A Antigens/metabolism MH - HLA-DR Antigens/metabolism MH - Humans MH - Hyperglycemia/immunology/*therapy MH - Insulin-Secreting Cells/metabolism MH - Interferon-gamma/immunology/metabolism MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/immunology/*metabolism MH - Phenotype MH - Rats MH - Umbilical Cord/*cytology PMC - PMC3896453 EDAT- 2013/12/04 06:00 MHDA- 2014/09/19 06:00 PMCR- 2013/11/28 CRDT- 2013/12/04 06:00 PHST- 2013/08/12 00:00 [received] PHST- 2013/11/19 00:00 [accepted] PHST- 2013/12/04 06:00 [entrez] PHST- 2013/12/04 06:00 [pubmed] PHST- 2014/09/19 06:00 [medline] PHST- 2013/11/28 00:00 [pmc-release] AID - ijmm-33-02-0263 [pii] AID - 10.3892/ijmm.2013.1572 [doi] PST - ppublish SO - Int J Mol Med. 2014 Feb;33(2):263-70. doi: 10.3892/ijmm.2013.1572. Epub 2013 Nov 28.