title: Bone marrow-derived mesenchymal stromal cells support rat pancreatic islet survival and insulin secretory function in vitro.
abstract: OBJECTIVE
  Recent evidence has suggested that transplanted bone marrow (BM)-derived mesenchymal stromal cells (MSC) are able to engraft and repair non-hematopoietic tissues successfully, including central nervous system, renal, pulmonary and skin tissue, and may possibly contribute to tissue regeneration. We examined the cytoprotective effect of BM MSC on co-cultured, isolated pancreatic islets.
  
  
  METHODS
  Pancreatic islets and MSC isolated from Lewis rats were divided into four experimental groups: (a) islets cultured alone (islet control); (b) islets cultured in direct contact with MSC (IM-C); (c) islets co-cultured with MSC in a Transwell system, which allows indirect cell contact through diffusible media components (IM-I); and (d) MSC cultured alone (MSC control). The survival and function of islets were measured morphologically and by analyzing insulin secretion in response to glucose challenge. Cytokine profiles were determined using a cytokine array and enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Islets contact-cultured with MSC (IM-C) showed sustained survival and retention of glucose-induced insulin secretory function. In addition, the levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were decreased, and tissue inhibitor of metalloproteinases-1 (TIMP-1) and vascular endothelial growth factor (VEGF) levels were increased at 4 weeks in both the IM-C and IM-I groups.
  
  
  CONCLUSIONS
  These results indicate that contact co-culture is a major factor that contributes to islet survival, maintenance of cell morphology and insulin function. There might also be a synergic effect resulting from the regulation of inflammatory cytokine production. We propose that BM MSC are suitable for generating a microenvironment favorable for the repair and longevity of pancreatic islets.
authors.affiliation: Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jung
authors.forename: Song-Cheol
authors.initials: SC
authors.lastname: Kim
authors.forename: Yu-Mee
authors.initials: YM
authors.lastname: Wee
authors.forename: Yang-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Monica Young
authors.initials: MY
authors.lastname: Choi
authors.forename: Seong-Hee
authors.initials: SH
authors.lastname: Jeong
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Lee
authors.forename: Dong-Gyun
authors.initials: DG
authors.lastname: Lim
authors.forename: Duck-Jong
authors.initials: DJ
authors.lastname: Han
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002448:Cell Adhesion; D048430:Cell Shape; D002470:Cell Survival; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D017154:Stromal Cells / Q000166:cytology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D005934:Glucagon