title: Effects of Composition of Alginate-Polyethylene Glycol Microcapsules and Transplant Site on Encapsulated Islet Graft Outcomes in Mice.
abstract: Understanding the effects of capsule composition and transplantation site on graft outcomes of encapsulated islets will aid in the development of more effective strategies for islet transplantation without immunosuppression.
  
  
  
  Here, we evaluated the effects of transplanting alginate (ALG)-based microcapsules (Micro) in the confined and well-vascularized epididymal fat pad (EFP) site, a model of the human omentum, as opposed to free-floating in the intraperitoneal cavity (IP) in mice. We also examined the effects of reinforcing ALG with polyethylene glycol (PEG). To allow transplantation in the EFP site, we minimized capsule size to 500 ± 17 μm. Unlike ALG, PEG resists osmotic stress, hence we generated hybrid microcapsules by mixing PEG and ALG (MicroMix) or by coating ALG capsules with a 15 ± 2 μm PEG layer (Double).
  
  
  
  We found improved engraftment of fully allogeneic BALB/c islets in Micro capsules transplanted in the EFP (median reversal time [MRT], 1 day) versus the IP site (MRT, 5 days; P < 0.01) in diabetic C57BL/6 mice and of Micro encapsulated (MRT, 8 days) versus naked (MRT, 36 days; P < 0.01) baboon islets transplanted in the EFP site. Although in vitro viability and functionality of islets within MicroMix and Double capsules were comparable to Micro, addition of PEG to ALG in MicroMix capsules improved engraftment of allogeneic islets in the IP site, but resulted deleterious in the EFP site, probably due to lower biocompatibility.
  
  
  
  Our results suggest that capsule composition and transplant site affect graft outcomes through their effects on nutrient availability, capsule stability, and biocompatibility.
authors.affiliation: 1 Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL. 2 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 3 Department of Pathophysiology and Transplantation, Universitá degli Studi di Milano, Milan, Italy. 4 Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy. 5 Department of Biomedical Engineering, University of Miami, Miami, FL. 6 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL. 7 Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL. 8 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Vita
authors.initials: V
authors.lastname: Manzoli
authors.forename: Maria M
authors.initials: MM
authors.lastname: Abreu
authors.forename: Connor A
authors.initials: CA
authors.lastname: Verheyen
authors.forename: Michael
authors.initials: M
authors.lastname: Seskin
authors.forename: Mejdi
authors.initials: M
authors.lastname: Najjar
authors.forename: R Damaris
authors.initials: RD
authors.lastname: Molano
authors.forename: Yvan
authors.initials: Y
authors.lastname: Torrente
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Alice A
authors.initials: AA
authors.lastname: Tomei
mesh_terms: D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D002214:Capsules; D004822:Epididymis; D020723:Glucuronic Acid / Q000008:administration & dosage; D006603:Hexuronic Acids / Q000008:administration & dosage; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009852:Omentum; D017063:Outcome Assessment, Health Care; D011092:Polyethylene Glycols / Q000008:administration & dosage*
chemical_list: D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D011092:Polyethylene Glycols; D020723:Glucuronic Acid