title: miR-410 enhanced hESC-derived pancreatic endoderm transplant to alleviate gestational diabetes mellitus.
abstract: Gestational diabetes mellitus (GDM) is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal mal-development. The deficit and dysfunction of insulin secreting β-cells are signature symptoms for GDM. Pancreatic progenitors derived from human embryonic stem cells (hESCs) were shown to be able to effectively treat diabetes in mice. In this study, we first identified that microRNA-410 (miR-410) directly targets lactate dehydrogenase A (LDHA), a gene selectively repressed in normal insulin secreting β-cells. hESCs that can be induced to express miR-410 hence keeping LDHA levels in check were then differentiated in vitro into pancreatic endoderm, followed by transplantation into db/+ mouse model of GDM. The transplant greatly improved glucose metabolism and reproductive outcome of the pregnant females suffering from GDM. Our findings describe for the first time the method of combining miRNA with hESCs, providing proof of concept by employing genetically modified stem cell therapy for treating GDM.
authors: Obstetrical DepartmentNorthwest Women's and Children's Hospital, 1616 Yanxiang Road, Xi'an, Shanxi Province 710061, ChinaDepartment of Obstetrics and GynecologyThe First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, 277 Yanta West Road, Xi'an, Shanxi Province 710061, China miyangmm@163.com hp752000@163.com.
authors: Yang
authors: Y
authors: Mi
authors: Obstetrical DepartmentNorthwest Women's and Children's Hospital, 1616 Yanxiang Road, Xi'an, Shanxi Province 710061, ChinaDepartment of Obstetrics and GynecologyThe First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, 277 Yanta West Road, Xi'an, Shanxi Province 710061, China.
authors: Na
authors: N
authors: Guo
authors: Obstetrical DepartmentNorthwest Women's and Children's Hospital, 1616 Yanxiang Road, Xi'an, Shanxi Province 710061, ChinaDepartment of Obstetrics and GynecologyThe First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, 277 Yanta West Road, Xi'an, Shanxi Province 710061, China.
authors: Tongqiang
authors: T
authors: He
authors: Obstetrical DepartmentNorthwest Women's and Children's Hospital, 1616 Yanxiang Road, Xi'an, Shanxi Province 710061, ChinaDepartment of Obstetrics and GynecologyThe First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, 277 Yanta West Road, Xi'an, Shanxi Province 710061, China.
authors: Jing
authors: J
authors: Ji
authors: Obstetrical DepartmentNorthwest Women's and Children's Hospital, 1616 Yanxiang Road, Xi'an, Shanxi Province 710061, ChinaDepartment of Obstetrics and GynecologyThe First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, 277 Yanta West Road, Xi'an, Shanxi Province 710061, China.
authors: Zhibin
authors: Z
authors: Li
authors: Obstetrical DepartmentNorthwest Women's and Children's Hospital, 1616 Yanxiang Road, Xi'an, Shanxi Province 710061, ChinaDepartment of Obstetrics and GynecologyThe First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, 277 Yanta West Road, Xi'an, Shanxi Province 710061, China miyangmm@163.com hp752000@163.com.
authors: Pu
authors: P
authors: Huang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015415:Biomarkers; D001823:Body Composition; D002454:Cell Differentiation; D002460:Cell Line; D016640:Diabetes, Gestational / Q000097:blood / Q000235:genetics* / Q000628:therapy; D004195:Disease Models, Animal; D004707:Endoderm / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics; D006946:Hyperinsulinism / Q000097:blood / Q000235:genetics / Q000628:therapy; D007328:Insulin / Q000097:blood / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D045022:Lactate Dehydrogenases / Q000737:chemistry / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D016035:Pancreas Transplantation; D011247:Pregnancy; D034622:RNA Interference; D012098:Reproduction
chemical_list: D020413:3' Untranslated Regions; D015415:Biomarkers; D007328:Insulin; C568527:MIRN410 microRNA, human; D035683:MicroRNAs; D045022:Lactate Dehydrogenases; C071195:D-lactate dehydrogenase; D005947:Glucose
keywords: C57BL/KsJ-Lepdb/+ mouse; gestational diabetes mellitus; human embryonic stem cell; microRNA-410; pancreatic endoderm