A novel approach to xenotransplantation combining surface engineering and genetic modification of isolated adult porcine islets

Surgery
Juan L ContrerasDevin E Eckhoff

Abstract

Effective cytoprotection to xenoislets would circumvent the major tissue limitation for pancreatic islet transplantation (PIT). Cell-surface engineering with poly[ethylene glycol] (PEG) derivatives can successfully prevent antibody binding to the surface antigens. Gene transfer of the antiapoptotic Bcl-2 gene has been shown to decrease cytotoxicity mediated by xenoreactive natural antibodies and complement. In this study, we assessed survival and function of surface-engineered porcine islets genetically modified to overexpress Bcl-2. Incorporation of PEG derivatives into the islet surface and adenovirus-mediated gene transfer of Bcl-2 (AdBcl-2) was accomplished within 24 hours post-isolation. Cytotoxicity induced by human xenoreactive natural antibodies was evaluated by islet intracellular lactate dehydrogenase release and microscopic analysis using membrane-integrity staining. Islet functionality was assessed by static incubation and after intraportal infusion (5000 IEQ) into diabetic NOD-SCID mice reconstituted with human lymphocytes (5 x 10 8 /intraperitoneally/15 days before PIT). No significant change in islet viability, morphology, and functionality was demonstrated after the incorporation of PEG-mono-succimidyl-succinate...Continue Reading

References

Nov 19, 1994·Lancet·C G GrothA Andersson
Nov 27, 1994·Transplantation·W HamelmannP J Morris
Sep 1, 1996·Nature Biotechnology·R P LanzaW L Chick
Sep 29, 1999·Immunology Today·M P SoaresF H Bach
May 19, 2000·Biomaterials·J L PanzaA J Russell
Jan 5, 2001·BMJ : British Medical Journal·P SerupT Mandrup-Poulsen
Sep 24, 2002·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Anthony Dorling
Dec 6, 2002·The Journal of Clinical Endocrinology and Metabolism·Boaz HirshbergDavid M Harlan

❮ Previous
Next ❯

Citations

Apr 9, 2008·Nanomedicine·Zhaoyang Ye, Ram I Mahato
Jan 17, 2013·World Journal of Gastroenterology : WJG·Denis Dufrane, Pierre Gianello
Jun 9, 2005·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Gary AdamsYuxin Cui
Dec 16, 2004·Xenotransplantation·Reto M Baertschiger, Leo H Buhler
Jan 28, 2010·Acta Biomaterialia·John T WilsonElliot L Chaikof
Oct 20, 2009·Trends in Immunology·Bo NilssonKristina Nilsson Ekdahl
Jan 15, 2008·Biomaterials·Yuji TeramuraHiroo Iwata
Nov 21, 2007·Advanced Drug Delivery Reviews·John T Wilson, Elliot L Chaikof
Nov 27, 2007·Advanced Drug Delivery Reviews·Yi LaiThomas Linn
Jun 8, 2006·Xenotransplantation·C E PearceD A V Clements
Jun 20, 2006·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·D Y LeeY Byun
Mar 27, 2007·Xenotransplantation·Sarah L LondriganAndrew M Lew
Mar 30, 2013·Advanced Functional Materials·Veronika KozlovskayaEugenia Kharlampieva
Feb 6, 2014·Advanced Healthcare Materials·Hernán R RengifoCherie L Stabler
Dec 6, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dong Yun LeeYoungro Byun
May 21, 2015·Journal of Zhejiang University. Science. B·Hai-tao ZhuBo Wang
Nov 29, 2014·Nature Reviews. Drug Discovery·Omid VeisehRobert Langer
Apr 16, 2011·Journal of the American Chemical Society·John T WilsonElliot L Chaikof
Sep 1, 2008·Journal of Diabetes Science and Technology·John T Wilson, Elliot L Chaikof
Jan 18, 2018·Chemistry : a European Journal·Xiaobao BiChuan-Fa Liu
May 24, 2007·Tissue Engineering·Jonathan BeckKytai T Nguyen
May 23, 2006·Pharmacological Reviews·Ajit S Narang, Ram I Mahato
Feb 29, 2020·Biomaterials Science·Barbara Kupikowska-Stobba, Dorota Lewińska
May 21, 2019·Clinical Medicine Insights. Endocrinology and Diabetes·Varun PathakReinhold J Medina
Dec 14, 2018·Journal of Biological Engineering·Daniel Y LeeYoung-Wook Won
Mar 9, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Seong Ik JeonCheol-Hee Ahn
Feb 5, 2019·Advanced Drug Delivery Reviews·Alexander U ErnstMinglin Ma
May 11, 2010·ACS Applied Materials & Interfaces·Osamu InuiHiroo Iwata
Jan 13, 2018·Bioconjugate Chemistry·Peter Y LiHao Cheng
Nov 5, 2020·Bioconjugate Chemistry·Shambojit RoyAndrew P Goodwin

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.