title: A model utilizing adult murine stem cells for creation of personalized islets for transplantation.
abstract: Clinical islet cell transplantation has demonstrated great promise for diabetes treatment. Two major obstacles are the organ donor shortage and the immunoresponse. The purpose of this study was to create a model using the patient's own adult stem cell sources, possibly in combination with non-self cells, such as pancreatic, hepatic, or embryonic stem cells, to create "personalized" islets. We hypothesize that the reconstructed islets have the normal capability to produce insulin and glucagon with reduced immunoresponses after transplantation. Stem cells are a proliferating population of master cells that have the ability for self-renewal and multilineage differentiation. The recently developed photolithograph-based, biologic, microelectromechanic system (BioMEMS) technique supplies a useful tool for biomedical applications. Our lab has developed a novel method that integrates the adult stem cell and BioMEMS to reconstruct personalized islets. We selected islet-derived progenitor cells (IPC) for repairing and reconstructing STZ-diabetic islets. A6(+)/PYY(+) or A6(+)/ngn3(+) cells were selected to manipulate the neoislets. After 3 to 4 weeks in culture, the reconstructed cells formed islet-like clusters containing insulin or glucagon producing cells. The pilot results showed the ability of these reconstructed islets to correct hyperglycemia when transplanted into a STZ-diabetic isograft mouse model. Although several technical problems remain with the mouse model, namely, the difficulty to collect enough islets from a single mouse because of animal size, the mouse isograft model is suitable for personalized islet development.
authors.affiliation: Department of Surgery, Transplantation and Stem Cell Laboratories, School of Medicine. University of North Carolina at Chapel Hill, 27599-7052, USA. jian_wang@med.unc.edu
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: L J
authors.initials: LJ
authors.lastname: Song
authors.forename: D A
authors.initials: DA
authors.lastname: Gerber
authors.forename: J H
authors.initials: JH
authors.lastname: Fair
authors.forename: L
authors.initials: L
authors.lastname: Rice
authors.forename: M
authors.initials: M
authors.lastname: LaPaglia
authors.forename: K A
authors.initials: KA
authors.lastname: Andreoni
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D017930:Genes, Reporter; D005934:Glucagon / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology*
chemical_list: D007328:Insulin; D049452:Green Fluorescent Proteins; D005934:Glucagon