title: Mutual effect of subcutaneously transplanted human adipose-derived stem cells and pancreatic islets within fibrin gel.
abstract: While subcutaneous tissue has been proposed as a potential site for pancreatic islet transplantation, concern remains that the microvasculature of subcutaneous tissue is too poor to support transplanted islets. In an effort to overcome this limitation, we evaluated whether fibrin gel with human adipose-derived stem cells (hADSCs) and rat pancreatic islets could cure diabetes mellitus when transplanted into the subcutaneous space of diabetic mice. Subcutaneously co-transplanted islets and hADSCs showed normalization of the diabetic recipient's blood glucose levels. The result was enhanced by co-treatment of fibroblast growth factor-2 (FGF2) in the fibrin gel. The hADSCs enhanced islet viability after transplantation by secreting various growth factors that can protect islets from hypoxic damage. Afterward, hADSCs could maintain islet viability by recruiting new microvasculature nearby the transplanted islets via overexpression of vascular endothelial growth factor (VEGF). The hADSCs did not directly differentiate into endothelial cells (no detection of biomarkers of human endothelial cells), but showed evidence of differentiation toward insulin-secreting cells (detection of human insulin). Mice receiving islet transplantation alone did not become normoglycemic. Collectively, co-transplantation of fibrin gel with islets and hADSCs will expand the indications for islet transplant therapy and the potential clinical application of cell-based therapy.
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.forename: Min Jin
authors.initials: MJ
authors.lastname: Jung
authors.forename: Jung-Youn
authors.initials: JY
authors.lastname: Shin
authors.forename: Wan-Geun
authors.initials: WG
authors.lastname: La
authors.forename: Yong Hwa
authors.initials: YH
authors.lastname: Hwang
authors.forename: Min Jun
authors.initials: MJ
authors.lastname: Kim
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Lee
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy; D005337:Fibrin / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005782:Gels; D006801:Humans; D007515:Islets of Langerhans / Q000098:blood supply / Q000187:drug effects*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000254:growth & development; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D040521:Subcutaneous Tissue / Q000187:drug effects*; D014022:Tissue Survival / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005782:Gels; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D005337:Fibrin
keywords: Adipose-derived stem cells; Diabetes; Hypoxia; Pancreatic islets; Transplantation