title: Survival and function of transplanted islet cells on an in vivo, vascularized tissue engineering platform in the rat: A pilot study.
abstract: As in vivo tissue engineering of complex tissues and organs progresses, there is a need for an independently vascularized, alterable, and recoverable model. Current models of islet cell transplantation (release into the portal venous system, placement under the renal capsule, and microencapsulation) lack these qualities. We have developed a model of angiogenesis and spontaneous tissue generation in the rat that lends itself as a potential platform for tissue engineering. In this experiment, we examined the effectiveness of such a model in addressing some of the shortcomings of endocrine pancreatic transplantation. An arteriovenous loop was created in the groins of five adult inbred Sprague-Dawley rats, and placed within polycarbonate chambers. Isolated pancreatic islet cell clusters were placed within the chambers, suspended in a matrix of Matrigel. The chambers were recovered at 3 weeks, and the newly generated tissue was processed for histologic and immunohistochemical analysis. By 3 weeks, spontaneous generation of angiogenesis and collagen matrix and deposition of a collagen matrix was observed. Surviving islet cells were identified by histology and their viability was confirmed via immunohistochemistry for insulin and glucagon. This study demonstrates the ability to maintain viability and functionality of transplanted islet cells on a tissue-engineered platform with an independent vascular supply. The model provides the ability to alter the graft environment via matrix substitution, cellular coculture, and administration of growth factors. The transplanted tissues are recoverable without animal sacrifice and are microsurgically transferable. This model may provide an in vivo culture platform for the study of islet transplantation.
authors.affiliation: Bernard O'Brien Institute of Microsurgery and the Department of Surgery, University of Melbourne, St. Vincent's Hospital, Melbourne, Australia. davbrown@umich.edu
authors.forename: David L
authors.initials: DL
authors.lastname: Brown
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meagher
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Knight
authors.forename: Effie
authors.initials: E
authors.lastname: Keramidaris
authors.forename: Rosalind
authors.initials: R
authors.lastname: Romeo-Meeuw
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Penington
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Morrison
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D005934:Glucagon / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000098:blood supply / Q000166:cytology / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D007328:Insulin; D005934:Glucagon