Local, Controlled Release In Vivo of Vascular Endothelial Growth Factor Within a Subcutaneous Scaffolded Islet Implant Reduces Early Islet Necrosis and Improves Performance of the Graft

Cell Transplantation
John A GebeRobert B Vernon

Abstract

Islet transplantation remains the only alternative to daily insulin therapy for control of type 1 diabetes (T1D) in humans. To avoid the drawbacks of intrahepatic islet transplantation, we are developing a scaffolded islet implant to transplant islets into nonhepatic sites. The implant test bed, sized for mice, consists of a limited (2-mm) thickness, large-pore polymeric sponge scaffold perforated with peripheral cavities that contain islets suspended in a collagen hydrogel. A central cavity in the scaffold holds a 2-mm diameter alginate sphere for controlled release of the angiogenic cytokine vascular endothelial growth factor ( VEGF). Host microvessels readily penetrate the scaffold and collagen gel to vascularize the islets. Here, we evaluate the performance of the implant in a subcutaneous (SC) graft site. Implants incorporating 500 syngeneic islets reversed streptozotocin-induced diabetes in mice approximately 30 d after SC placement. Controlled release of a modest quantity (20 ng) of VEGF within the implant significantly reduced the time to normoglycemia compared to control implants lacking VEGF. Investigation of underlying causes for this effect revealed that inclusion of 20 ng of VEGF in the implants significantly reduc...Continue Reading

References

Jun 15, 1996·Transplantation·J H JuangG C Weir
Apr 9, 1998·Transplantation Proceedings·R M JindalS E Fineberg
Nov 13, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·P M BeckerJ G Garcia
Jan 14, 2003·Matrix Biology : Journal of the International Society for Matrix Biology·Robert B Vernon, Michel D Gooden
Mar 5, 2003·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Tatsuya KinRay V Rajotte
Apr 3, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·T LinnR G Bretzel
Jun 15, 2004·Transplantation Proceedings·J StagnerR Parthasarathy
Nov 22, 2005·Transplantation Proceedings·J-H JuangC-H Kuo
Dec 11, 2007·Archives of Medical Research·Anastasio Salazar-BañuelosLuis Benítez-Bribiesca
Apr 22, 2008·American Journal of Surgery·Anastasio Salazar-BañuelosLuis Benítez-Bribiesca
May 6, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Elsa LaughlinGerald Nepom
Dec 24, 2008·Transplantation·Rodolfo AlejandroUNKNOWN Collaborative Islet Transplant Registry Investigators
Apr 28, 2009·The Journal of Surgical Research·Thomas R HeftyCarla J Greenbaum
Jun 30, 2009·Tissue Engineering. Part a·Alan J HusseySandra J Feeney
Oct 23, 2009·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·O ErikssonT Lundgren
Feb 2, 2010·Journal of Korean Medical Science·Hyoung-Il KimSang-Joon Kim
Apr 24, 2010·Immunity·Anette-G Ziegler, Gerald T Nepom
Jul 29, 2010·Current Diabetes Reports·Amer Rajab
Dec 9, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Byung Wan LeeSung-Hee Ihm
Jul 5, 2012·Cold Spring Harbor Perspectives in Medicine·Michael McCall, A M James Shapiro
Sep 4, 2013·Diabetes/metabolism Research and Reviews·Naoaki SakataMichiaki Unno
Feb 15, 2014·Advances in Wound Care·Sadanori AkitaAkiyoshi Hirano
Jun 10, 2014·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·N M Luan, H Iwata
Apr 22, 2015·Nature Biotechnology·Andrew R PepperA M James Shapiro
Sep 10, 2016·The Journal of Clinical Endocrinology and Metabolism·R Paul Robertson
May 10, 2017·Biomaterials·Mijke BuitingaAart van Apeldoorn

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Citations

Feb 23, 2019·Journal of Biomaterials Applications·Liancheng XuZhiwei Wang
Oct 4, 2018·Current Diabetes Reports·Antonio Citro, Harald C Ott
Sep 16, 2020·Transplantation Proceedings·Lingling WeiDong Zhao
Nov 22, 2020·International Journal of Molecular Sciences·Felipe ArroyaveFernando Lizcano
Apr 26, 2021·Biomaterials·Jorge Santini-GonzálezEdward A Phelps

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Methods Mentioned

BETA
biopsy
dissection
blood draw

Software Mentioned

Prism®
ImageJ
GraphPad

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