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Cytoprotection of PEG-modified adult porcine pancreatic islets for improved xenotransplantation.

Publication ,  Journal Article
Xie, D; Smyth, CA; Eckstein, C; Bilbao, G; Mays, J; Eckhoff, DE; Contreras, JL
Published in: Biomaterials
February 2005

Functional poly(ethylene glycol) (PEG) derivatives, including monosuccinimidyl PEG (MSPEG) with molecular weight (MW) of 2000 (2 kDa) as well as 5 kDa and disuccinimidyl PEG (DSPEG) with MW of 3 and 6 kDa, were synthesized and characterized. They were used to modify the surface of adult porcine islets for cytoprotection. The islets were isolated, purified and modified with functional PEG. Untreated porcine islets were used as control. An in vitro human antibody/complement-mediated cytotoxicity test based on the release of intracellular lactate dehydrogenase was used to evaluate cytotoxicity of human serum to the modified islets. In vitro cell viability was assessed using membrane-integrity straining and islet metabolism in culture. In vitro islet functionality was evaluated by glucose-stimulated insulin release of islets in static incubation with human serum. In vivo islet functionality was evaluated by monitoring non-fasting blood glucose level in streptozotocin-induced diabetic (SCID) immunocompromized mice after intraportal transplantation of porcine islets. Results show that all the PEG derivatives used in the study showed significant in vitro and in vivo cytoprotections against cytotoxic effects elicited by human serum and diabetic SCID mice, respectively, to porcine islets. DSPEG derivatives combined with human albumin exhibited a better cytoprotection, as compared to MSPEG ones, due to the capacity of the succinimidyl groups to selectively react with amino groups of the albumin under physiological conditions. The effects of both MW and concentration of the PEG derivatives on cytoprotection were significant. It appears that this novel biotechnology will be an attractive approach for improved xenotransplantation of islets.

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Published In

Biomaterials

DOI

ISSN

0142-9612

Publication Date

February 2005

Volume

26

Issue

4

Start / End Page

403 / 412

Location

Netherlands

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Engineering
  • Polyethylene Glycols
  • Pancreas, Artificial
  • Mice, SCID
  • Mice
  • Materials Testing
  • Male
  • Islets of Langerhans Transplantation
  • Islets of Langerhans
 

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Xie, D., Smyth, C. A., Eckstein, C., Bilbao, G., Mays, J., Eckhoff, D. E., & Contreras, J. L. (2005). Cytoprotection of PEG-modified adult porcine pancreatic islets for improved xenotransplantation. Biomaterials, 26(4), 403–412. https://doi.org/10.1016/j.biomaterials.2004.02.048
Xie, Dong, Cheryl A. Smyth, Christopher Eckstein, Guadalupe Bilbao, Jimmy Mays, Devin E. Eckhoff, and Juan L. Contreras. “Cytoprotection of PEG-modified adult porcine pancreatic islets for improved xenotransplantation.Biomaterials 26, no. 4 (February 2005): 403–12. https://doi.org/10.1016/j.biomaterials.2004.02.048.
Xie D, Smyth CA, Eckstein C, Bilbao G, Mays J, Eckhoff DE, et al. Cytoprotection of PEG-modified adult porcine pancreatic islets for improved xenotransplantation. Biomaterials. 2005 Feb;26(4):403–12.
Xie, Dong, et al. “Cytoprotection of PEG-modified adult porcine pancreatic islets for improved xenotransplantation.Biomaterials, vol. 26, no. 4, Feb. 2005, pp. 403–12. Pubmed, doi:10.1016/j.biomaterials.2004.02.048.
Xie D, Smyth CA, Eckstein C, Bilbao G, Mays J, Eckhoff DE, Contreras JL. Cytoprotection of PEG-modified adult porcine pancreatic islets for improved xenotransplantation. Biomaterials. 2005 Feb;26(4):403–412.
Journal cover image

Published In

Biomaterials

DOI

ISSN

0142-9612

Publication Date

February 2005

Volume

26

Issue

4

Start / End Page

403 / 412

Location

Netherlands

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Engineering
  • Polyethylene Glycols
  • Pancreas, Artificial
  • Mice, SCID
  • Mice
  • Materials Testing
  • Male
  • Islets of Langerhans Transplantation
  • Islets of Langerhans