title: Combined transfection of the three transcriptional factors, PDX-1, NeuroD1, and MafA, causes differentiation of bone marrow mesenchymal stem cells into insulin-producing cells.
abstract: OBJECTIVE
  The goal of cell transcription for treatment of diabetes is to generate surrogate β-cells from an appropriate cell line. However, the induced replacement cells have showed less physiological function in producing insulin compared with normal β-cells.
  
  
  METHODS
  Here, we report a procedure for induction of insulin-producing cells (IPCs) from bone marrow murine mesenchymal stem cells (BM-mMSCs). These BM-mMSCs have the potential to differentiate into insulin-producing cells when a combination of PDX-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation-1), and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) genes are transfected into them and expressed in these cells.
  
  
  RESULTS
  Insulin biosynthesis and secretion were induced in mMSCs into which these three genes have been transfected and expressed. The amount of induced insulin in the mMSCs which have been transfected with the three genes together is significantly higher than in those mMSCs that were only transfected with one or two of these three genes. Transplantation of the transfected cells into mice with streptozotocin-induced diabetes results in insulin expression and the reversal of the glucose challenge.
  
  
  CONCLUSIONS
  These findings suggest major implications for cell replacement strategies in generation of surrogate β-cells for the treatment of diabetes.
authors: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors: Qing-Song
authors: QS
authors: Guo
authors: Ming-Yan
authors: MY
authors: Zhu
authors: Lei
authors: L
authors: Wang
authors: Xiang-Jun
authors: XJ
authors: Fan
authors: Yu-Hua
authors: YH
authors: Lu
authors: Zhi-Wei
authors: ZW
authors: Wang
authors: Sha-Jun
authors: SJ
authors: Zhu
authors: Yao
authors: Y
authors: Wang
authors: Yan
authors: Y
authors: Huang
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D017690:Cell Transplantation; D003920:Diabetes Mellitus / Q000378:metabolism; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology; D051473:Maf Transcription Factors, Large / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D051473:Maf Transcription Factors, Large; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C485160:Mafa protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein; C093564:Neurogenic differentiation factor 1