PMID- 21142900 OWN - NLM STAT- MEDLINE DCOM- 20110316 LR - 20181217 IS - 1477-2566 (Electronic) IS - 1465-3249 (Linking) VI - 13 IP - 1 DP - 2011 Jan TI - Bone marrow-derived mesenchymal stromal cells support rat pancreatic islet survival and insulin secretory function in vitro. PG - 19-29 LID - 10.3109/14653249.2010.518608 [doi] AB - BACKGROUND AIMS: 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-alpha (TNF-alpha) 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. FAU - Jung, Eun-Jung AU - Jung EJ AD - Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea. FAU - Kim, Song-Cheol AU - Kim SC FAU - Wee, Yu-Mee AU - Wee YM FAU - Kim, Yang-Hee AU - Kim YH FAU - Choi, Monica Young AU - Choi MY FAU - Jeong, Seong-Hee AU - Jeong SH FAU - Lee, Jiyeon AU - Lee J FAU - Lim, Dong-Gyun AU - Lim DG FAU - Han, Duck-Jong AU - Han DJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cytotherapy JT - Cytotherapy JID - 100895309 RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Insulin) RN - 9007-92-5 (Glucagon) SB - IM MH - Animals MH - Bone Marrow Cells/*cytology MH - Cell Adhesion MH - Cell Shape MH - Cell Survival MH - Coculture Techniques MH - Cytokines/metabolism MH - Glucagon/metabolism MH - Inflammation Mediators/metabolism MH - Insulin/*metabolism MH - Insulin Secretion MH - Islets of Langerhans/*cytology/*metabolism MH - Mesenchymal Stem Cells/*cytology/metabolism MH - Phenotype MH - Rats MH - Rats, Inbred Lew MH - Stromal Cells/cytology EDAT- 2010/12/15 06:00 MHDA- 2011/03/17 06:00 CRDT- 2010/12/15 06:00 PHST- 2010/12/15 06:00 [entrez] PHST- 2010/12/15 06:00 [pubmed] PHST- 2011/03/17 06:00 [medline] AID - S1465-3249(11)70477-7 [pii] AID - 10.3109/14653249.2010.518608 [doi] PST - ppublish SO - Cytotherapy. 2011 Jan;13(1):19-29. doi: 10.3109/14653249.2010.518608.