title: Naringenin enhances the efficacy of human embryonic stem cell-derived pancreatic endoderm in treating gestational diabetes mellitus mice.
abstract: Gestational diabetes mellitus (GDM) is a disease commonly occurs during mid to late pregnancy with pathologies such as hyperglycemia, hyperinsulinemia and mal-development of fetus. We have previously demonstrated that pancreatic endoderm (PE) derived from human embryonic stem cells (hESCs) effectively alleviated diabetic symptoms in a mouse model of GDM, although the clinical efficacy was limited due to oxidative stress. In this study, using the anti-oxidant agent naringenin, we aimed to further enhance the efficacy of hESC-derived PE transplant. Insulin-secreting PE was differentiated from hESCs, which were then transplanted into GDM mice. Naringenin was administered to mice receiving the PE transplant, with sham operated mice serving as negative control, to assess its effect on alleviation of GDM symptoms. We found that naringenin supplement further improved insulin response, glucose metabolism and reproductive outcome of the PE-transplanted female mice. Our new findings further potentiates the feasibility of using differentiated hESCs to treat GDM, in which anti-oxidative agent such as naringenin could greatly enhance the clinical efficacy of stem cell based therapies.
authors.affiliation: Teaching and Research Section of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Bao-Heng
authors.initials: BH
authors.lastname: Xing
authors.affiliation: The Second Department of Obstetrics, Cangzhou City Central Hospital, Cangzhou 061001, China.
authors.forename: Feng-Zhen
authors.initials: FZ
authors.lastname: Yang
authors.affiliation: Teaching and Research Section of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang 050011, China. Electronic address: xiaohuawu1234@163.com.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Wu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016640:Diabetes, Gestational / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D004707:Endoderm / Q000637:transplantation*; D005260:Female; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D000066449:Human Embryonic Stem Cells / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008098:Litter Size; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D044950:Flavanones; D007328:Insulin; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C005273:naringenin
keywords: C57BL/KsJ-Lep(db/+) mouse; Gestational diabetes mellitus; Human embryonic stem cells; Insulin-secreting pancreatic endoderm; Naringenin