title: Umbilical cord mesenchymal stem cells are able to undergo differentiation into functional islet-like cells in type 2 diabetic tree shrews.
abstract: Islet transplantation is arguably one of the most promising strategies to treat patients suffering with diabetes mellitus. However, a combination of a lack of donors and chronic immune rejection limit clinical applications. Here, we evaluated the efficacy of cell therapy using islet-like cells differentiated from umbilical cord mesenchymal stem cells (UC-MSCs) of tree shrews for the treatment of type 2 diabetes. Enhanced green fluorescent protein (eGFP) labeled UC-MSCs were directly injected into type 2 diabetic tree shrews, where UC-MSC differentiated into functional islet-like cells and alleviated disease severity, as evidenced by improved biochemical features and reduced concentrations of inflammatory cytokines. We also demonstrated that in vitro culture of UC-MSCs for six days in a high-glucose environment (40 mmol/L or 60 mmol/L glucose) resulted in significant gene methylation. The potency of UC-MSCs differentiated into insulin-secreting cells was attributed to the activation of Notch signal pathways. This study provides evidence that cell therapy of islet-like cells differentiated from UC-MSCs is a feasible, simple and inexpensive approach in the treatment of type 2 diabetes.
authors.affiliation: Cell Biological Therapy Center of Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan Province, China; The Nation and Region Integrated Engineering Laboratory of Stem Cell and Immunocyte Biological Technology, Kunming, Yunnan Province, China; Key Laboratory of Translational Medicine of Cell Therapy Technology of Yunnan Province, Kunming, Yunnan, China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Pan
authors.affiliation: Cell Biological Therapy Center of Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan Province, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Key Laboratory of Translational Medicine of Cell Therapy Technology of Yunnan Province, Kunming, Yunnan, China.
authors.forename: Guang-Ping
authors.initials: GP
authors.lastname: Ruan
authors.affiliation: Cell Biological Therapy Center of Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan Province, China; The Nation and Region Integrated Engineering Laboratory of Stem Cell and Immunocyte Biological Technology, Kunming, Yunnan Province, China; Key Laboratory of Translational Medicine of Cell Therapy Technology of Yunnan Province, Kunming, Yunnan, China.
authors.forename: Rong-Qing
authors.initials: RQ
authors.lastname: Pang
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650093, Yunnan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Cell Biological Therapy Center of Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan Province, China.
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Key Laboratory of Translational Medicine of Cell Therapy Technology of Yunnan Province, Kunming, Yunnan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: The Nation and Region Integrated Engineering Laboratory of Stem Cell and Immunocyte Biological Technology, Kunming, Yunnan Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Cell Biological Therapy Center of Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan Province, China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Cai
authors.affiliation: Department of Occupational Medicine, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, Guangdong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Translational Medicine of Cell Therapy Technology of Yunnan Province, Kunming, Yunnan, China. Electronic address: chenyidoctor@sohu.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cell Biological Therapy Center of Kunming General Hospital of Chengdu Military Command, Kunming, Yunnan Province, China; The Nation and Region Integrated Engineering Laboratory of Stem Cell and Immunocyte Biological Technology, Kunming, Yunnan Province, China; Key Laboratory of Translational Medicine of Cell Therapy Technology of Yunnan Province, Kunming, Yunnan, China. Electronic address: qing1021zhu@163.com.
authors.forename: Xiang-Qing
authors.initials: XQ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014418:Tupaiidae / Q000502:physiology*; D014470:Umbilical Cord / Q000502:physiology*
keywords: Diabetes; Insulin-secreting cells; Mesenchymal stem cells; Umbilical cord