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 language | English |
|---|---|
| Pages (from-to) | 1061-1070 |
| Number of pages | 10 |
| Journal | Advanced healthcare materials |
| Volume | 3 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jan 1 2014 |
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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 journal › Article
}
TY - JOUR
T1 - Long-term survival of allograft murine islets coated via covalently stabilized polymers
AU - Rengifo, Hernán R.
AU - Giraldo, Jaime A.
AU - Labrada, Irayme
AU - Stabler, Cherie L.
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Alginates
KW - Encapsulation
KW - Immunomodulation
KW - Poly(ethylene glycol)
KW - Staudinger ligation
UR - http://www.scopus.com/inward/record.url?scp=84904035628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904035628&partnerID=8YFLogxK
U2 - 10.1002/adhm.201300573
DO - 10.1002/adhm.201300573
M3 - Article
AN - SCOPUS:84904035628
VL - 3
SP - 1061
EP - 1070
JO - Advanced healthcare materials
JF - Advanced healthcare materials
SN - 2192-2640
IS - 7
ER -