title: Exendin-4 enhances the differentiation of Wharton's jelly mesenchymal stem cells into insulin-producing cells through activation of various β-cell markers.
abstract: Diabetes mellitus is a devastating metabolic disease. Generation of insulin-producing cells (IPCs) from stem cells, especially from Wharton's jelly mesenchymal stem cells (WJ-MSCs), has sparked much interest recently. Exendin-4 has several beneficial effects on MSCs and β cells. However, its effects on generation of IPCs from WJ-MSCs specifically have not been studied adequately. The purpose of this study was therefore to investigate how exendin-4 could affect the differentiation outcome of WJ-MSCs into IPCs, and to investigate the role played by exendin-4 in this differentiation process.
  
  
  
  WJ-MSCs were isolated, characterized and then induced to differentiate into IPCs using two differentiation protocols: protocol A, without exendin-4; and protocol B, with exendin-4. Differentiated IPCs were assessed by the expression of various β-cell-related markers using quantitative RT-PCR, and functionally by measuring glucose-stimulated insulin secretion.
  
  
  
  The differentiation protocol B incorporating exendin-4 significantly boosted the expression levels of β-cell-related genes Pdx-1, Nkx2.2, Isl-1 and MafA. Moreover, IPCs generated by protocol B showed much better response to variable glucose concentrations as compared with those derived from protocol A, which totally lacked such response. Furthermore, exendin-4 alone induced early differentiation markers such as Pdx-1 and Nkx2.2 but not Isl-1, besides inducing late markers such as MafA. In addition, exendin-4 showed a synergistic effect with nicotinamide and β-mercaptoethanol in the induction of these markers.
  
  
  
  Exendin-4 profoundly improves the differentiation outcome of WJ-MSCs into IPCs, possibly through the ability to induce the expression of β-cell markers.
authors: Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors: Dina H
authors: DH
authors: Kassem
authors: Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors: Mohamed M
authors: MM
authors: Kamal
authors: Gynecology and Obstetrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors: Abd El-Latif G
authors: Ael-L
authors: El-Kholy
authors: Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. hala.elmesallamy@hotmail.com.
authors: Hala O
authors: HO
authors: El-Mesallamy
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D000077270:Exenatide; D005947:Glucose / Q000378:metabolism; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008623:Mercaptoethanol / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D009687:Nuclear Proteins; D010455:Peptides / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors; D014688:Venoms / Q000494:pharmacology*; D059631:Wharton Jelly / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D007328:Insulin; C000715631:NKX2-2 protein, human; D009687:Nuclear Proteins; D010455:Peptides; D014157:Transcription Factors; D014688:Venoms; D009536:Niacinamide; D008623:Mercaptoethanol; D000077270:Exenatide; D005947:Glucose
keywords: Diabetes mellitus; Exendin-4; Insulin-producing cells; Mesenchymal stem cells; Wharton’s jelly