Long-term survival of allograft murine islets coated via covalently stabilized polymers

Hernán R. Rengifo, Jaime A. Giraldo, Irayme Labrada, Cherie L. Stabler

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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-2d) islets into streptozotozin-induced diabetic C57BL/6 (H-2b) 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. Application of bioorthogonal polymers for cellular encapsulation: Alginate and poly(ethylene glycol) (PEG), functionalized with azide and 1-methyl-2-diphenylphos-phino-terephthalate (MDT), respec-tively, form spontaneous and chemoselective crosslinks via the bioorthogonal Staudinger ligation scheme. These polymers are utilized to generate ultrathin coatings on murine pancreatic islets. Resulting coatings are nontoxic and impart significant immunoprotective effects when transplanted in a full allograft mismatch murine model.

Original languageEnglish
Pages (from-to)1061-1070
Number of pages10
JournalAdvanced healthcare materials
Volume3
Issue number7
DOIs
StatePublished - Jan 1 2014

Fingerprint

Allografts
Polymers
Coatings
Polyethylene glycols
phosphine
Azides
Ethylene Glycol
Islets of Langerhans
Ligation
Alginate
Islets of Langerhans Transplantation
Type 1 Diabetes Mellitus
Transplants
Insulin
Transplantation
Medical problems
Encapsulation
Glucose
Animals
Pharmaceutical Preparations

Keywords

  • Alginates
  • Encapsulation
  • Immunomodulation
  • Poly(ethylene glycol)
  • Staudinger ligation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Pharmaceutical Science

Cite this

Long-term survival of allograft murine islets coated via covalently stabilized polymers. / Rengifo, Hernán R.; Giraldo, Jaime A.; Labrada, Irayme; Stabler, Cherie L.

In: Advanced healthcare materials, Vol. 3, No. 7, 01.01.2014, p. 1061-1070.

Research output: Contribution to journalArticle

Rengifo, Hernán R. ; Giraldo, Jaime A. ; Labrada, Irayme ; Stabler, Cherie L. / Long-term survival of allograft murine islets coated via covalently stabilized polymers. In: Advanced healthcare materials. 2014 ; Vol. 3, No. 7. pp. 1061-1070.
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