title: Molecularly engineered islet cell clusters for diabetes mellitus treatment.
abstract: Pancreatic islet transplantation is a promising method for curing diabetes mellitus. We proposed in this study a molecularly engineered islet cell clusters (ICCs) that could overcome problems posed by islet transplantation circumstances and host's immune reactions. A gene containing  highly releasable exendin-4, an insulinotropic protein, was delivered into single islet cells to enhance glucose sensitivity; thereafter, the cells were reaggregated into small size ICCs. Then the surface of ICCs was modified with biocompatible poly(ethylene glycol)-lipid (PEG) (C18) for preventing  immune reactions. The regimen of ICCs with low doses of anti-CD154 mAb and tacrolimus could effectively maintain the normal glucose level in diabetic mice. This molecularly engineered PEG-Sp-Ex-4 ICC regimen prevented cell death in transplantation site, partly through improving the regulation  of glucose metabolism and by preventing hypoxia- and immune response-induced apoptosis. Application of this remedy is also potentially far-reaching; one would be to help overcome islet supply shortage due to the limited availability of pancreas donors and reduce the immunosuppressant regimens  to eliminate their adverse effects.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Simmyung
authors.initials: S
authors.lastname: Yook
authors.forename: Jee-Heon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Jung
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Bok Hyeon
authors.initials: BH
authors.lastname: Im
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Seo
authors.forename: Jun Beom
authors.initials: JB
authors.lastname: Park
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Ahn
authors.forename: Haeshin
authors.initials: H
authors.lastname: Lee
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Lee
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D023201:CD40 Ligand / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy*; D000077270:Exenatide; D005818:Genetic Engineering; D005947:Glucose / Q000378:metabolism; D000860:Hypoxia; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D016559:Tacrolimus / Q000494:pharmacology; D014688:Venoms / Q000235:genetics / Q000378:metabolism
chemical_list: D000906:Antibodies; D010455:Peptides; D014688:Venoms; D023201:CD40 Ligand; D011092:Polyethylene Glycols; D000077270:Exenatide; D005947:Glucose; D016559:Tacrolimus