Long-term survival of allograft murine islets coated via covalently stabilized polymers.
Clinical islet transplantation (CIT) has emerged as a promising treatment option for type 1 diabetes mellitus (T1DM); however, the antirejection drug regimen necessary to mitigate allograft islet rejection is undesirable. The use of polymeric coatings to immunocamouflage the transplant from host immune attack has great potential. Alginate and poly(ethylene glycol) (PEG)-based polymers, functionalized with azide and phosphine, respectively, which form spontaneous and chemoselective crosslinks via the bioorthogonal Staudinger ligation scheme, were recently developed. Here, the utility of these polymers to form immunoprotective, ultrathin coatings on murine primary pancreatic islets is explored. Resulting coatings are nontoxic, with unimpaired glucose stimulated insulin secretion. Transplantation of coated BALB/c (H-2(d) ) islets into streptozotozin-induced diabetic C57BL/6 (H-2(b) ) results in prompt achievement of normoglycemia, at a rate comparable to controls. A significant subset of animals receiving coated islets (57%) exhibits long-term (>100 d) function, with robust islets observed upon explantation. Control islets rejected after 15 d (±9 d). Results illustrate the capacity of chemoselectively functionalized polymers to form coatings on islets, imparting no detrimental effect to the underlying cells, with resulting coatings exhibiting significant protective effects in an allograft murine model.
Diabetes Research Institute, Leonard M. Miller School of Medicine, University of Miami, 1450 NW 10th Ave, Miami, FL, 33136, USA.
Hernán R
HR
Rengifo
Jaime A
JA
Giraldo
Irayme
I
Labrada
Cherie L
CL
Stabler
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects*; D007515:Islets of Langerhans / Q000187:drug effects; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*
D001672:Biocompatible Materials; D011092:Polyethylene Glycols
Staudinger ligation; alginates; encapsulation; immunomodulation; poly(ethylene glycol)