title: Mesenchymal stem cells contribute to insulin-producing cells upon microenvironmental manipulation in vitro.
abstract: BACKGROUND
  Extracellular microenvironment and intrinsic genetic programs determine the fate of stem cells. We observed whether mesenchymal stem cells (MSCs) contributed to insulin-producing cells in a manipulated microenvironment.
  
  
  METHODS
  We delivered pancreatic pieces into Niobium-Coated Dynamatrix to construct a simulated pancreatic microenvironment, upon which soluble cytokine exchange and direct cell-cell contact between MSCs and pancreatic cells could occur. Bone marrow-derived MSCs were cultured upon the microenvironment. Differentiated isletlike cells were observed under an inverted microscope. Insulin in supernates was measurement by enzyme-linked immunosorbent assay. Insulin and c-peptide expression were verified by fluorescent immunocytochemistry and fluorescence in situ hybridization. Apoptosis of isletlike masses in high-glucose DMEM was detected by FACS.
  
  
  RESULTS
  After 3 to 4 weeks in culture, typical isletlike masses were observed. Insulin secreted by differentiated cells (414.47+/-30.30 mIU/L) was much greater than that of undifferentiated cells (4.89+/-1.01 mIU/L; P<.05). Insulin and c-peptide expression were positive both in protein and mRNA levels. The transdifferentiated isletlike mass did not undergo apoptosis after another 3 weeks of culture in high-glucose DMEM.
  
  
  CONCLUSIONS
  This simulated injury microenvironment without induction guided MSCs to functional isletlike cells hopefully to replace beta cells.
authors: Department of Immunology Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: C
authors: C
authors: Chang
authors: D
authors: D
authors: Niu
authors: H
authors: H
authors: Zhou
authors: F
authors: F
authors: Li
authors: F
authors: F
authors: Gong
mesh_terms: D000818:Animals; D002096:C-Peptide / Q000032:analysis; D005269:Femur / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology; D045164:Mesenchymal Stem Cell Transplantation; D023421:Models, Animal; D010179:Pancreas / Q000166:cytology; D011817:Rabbits
chemical_list: D002096:C-Peptide; D007328:Insulin