title: Human umbilical cord-derived mesenchymal stem cells can secrete insulin in vitro and in vivo.
abstract: Diabetes mellitus is characterized by autoimmune destruction of pancreatic beta cells, leading to decreased insulin production. Differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells offers novel ways of diabetes treatment. MSCs can be isolated from the human umbilical cord tissue and differentiate into insulin-secreting cells. Human umbilical cord-derived stem cells (hUDSCs) were obtained after birth, selected by plastic adhesion, and characterized by flow cytometric analysis. hUDSCs were transduced with nonintegrated lentivirus harboring PDX1 (nonintegrated LV-PDX1) and was cultured in differentiation medium in 21 days. Pancreatic duodenum homeobox protein-1 (PDX1) is a transcription factor in pancreatic development. Significant expressions of PDX1, neurogenin3 (Ngn3), glucagon, glucose transporter2 (Glut2), and somatostatin were detected by quantitative RT-PCR (P < 0.05). PDX1 and insulin proteins were shown by immunocytochemistry analysis. Insulin secretion of hUDSCs(PDX1+) in the high-glucose medium was 1.8 μU/mL. They were used for treatment of diabetic rats and could decrease the blood glucose level from 400 mg/dL to a normal level in 4 days. In conclusion, our results demonstrated that hUDSCs are able to differentiate into insulin-producing cells by transduction with nonintegrated LV-PDX1. These hUDSCs(PDX1+) have the potential to be used as a viable resource in cell-based gene therapy of type 1 diabetes.
authors.affiliation: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Zahra Niki
authors.initials: ZN
authors.lastname: Boroujeni
authors.forename: Ahmad
authors.initials: A
authors.lastname: Aleyasin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000628:therapy*; D005434:Flow Cytometry; D015316:Genetic Therapy; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology*; D016086:Lentivirus; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D015534:Trans-Activators / Q000235:genetics; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein
keywords: PDX1; diabetes mellitus; hUDSCs; insulin-producing cells; nonintegrated lentiviruses