title: Adipose tissue-derived mesenchymal stromal cells efficiently differentiate into insulin-producing cells in pancreatic islet microenvironment both in vitro and in vivo.
abstract: OBJECTIVE
  Differentiation or reprogramming of stem cells could be achieved by remodulating the microenvironment, which regulates the fate of cells by soluble factors and contacts. By providing an in vivo-like microenvironment, directional and functional differentiation of stem cells could be achieved in vitro. In this study, the differentiation of mesenchymal stromal cells (MSCs) derived from rat tissues (adipose, rAT; bone marrow, rBM) were analyzed by in vitro and in vivo co-culture experiments. The insulin-producing capacities of islets transplanted under the renal kidney capsule with rAT- and rBM-MSCs were compared and the reduction of hyperglycemia symptoms in rat models was examined.
  
  
  METHODS
  MSCs prelabeled with green fluorescence protein were co-cultured with islets directly. The insulin production of cells was determined by immunostaining and ELISA. Streptozotocin-induced diabetic rat models were created and MSCs were co-transplanted with the islets under the kidney capsule to confirm the in vitro results.
  
  
  RESULTS
  MSCs were differentiated into insulin-producing cells after 38 days of co-culture, confirmed by insulin and C-peptide stainings. In vivo functional studies revealed that the co-culture of islets with MSCs provided higher differentiation efficiency. The weight gain measurement and glucose tolerance test in the rat group co-transplanted of rAT-MSCs and islets indicate a better recovery than islet-alone transplants and co-transplants of islets and rBM-MSCs.
  
  
  CONCLUSIONS
  rAT-MSCs could be considered as the cell of choice for cell-based treatment of type 1 diabetes. Because the co-transplantation of islets with MSCs increases the number of insulin-producing cells, this method was suggested for clinical applications.
authors: Kocaeli University, Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli, Turkey. ekaraoz@hotmail.com
authors: Erdal
authors: E
authors: Karaoz
authors: Alparslan
authors: A
authors: Okcu
authors: Zehra Seda
authors: ZS
authors: Ünal
authors: Cansu
authors: C
authors: Subasi
authors: Ozlem
authors: O
authors: Saglam
authors: Gokhan
authors: G
authors: Duruksu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D049452:Green Fluorescent Proteins; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D055153:Stem Cell Niche
chemical_list: D001786:Blood Glucose; D007328:Insulin; D049452:Green Fluorescent Proteins