| Autor: |
Najjar Mejdi, Manzoli Vita, Villa Chiara, Martino Mikaël M, Molano R Damaris, Torrente Yvan, Pileggi Antonello, Inverardi Luca, Ricordi Camillo, Hubbell Jeffrey A, Tomei Alice A |
| Rok vydání: |
2015 |
| Zdroj: |
Biotechnology and bioengineering |
| DOI: |
10.1002/bit.25589 |
| Popis: |
With a view toward reduction of graft loss we explored pancreatic islet transplantation within fibrin matrices rendered pro angiogenic by incorporation of minimal doses of vascular endothelial growth factor A165 and platelet derived growth factor BB presented complexed to a fibrin bound integrin binding fibronectin domain. Engineered matrices allowed for extended release of pro angiogenic factors and for their synergistic signaling with extracellular matrix binding domains in the post transplant period. Aprotinin addition delayed matrix degradation and prolonged pro angiogenic factor availability within the graft. Both subcutaneous (SC) and epididymal fat pad (EFP) sites were evaluated. We show that in the SC site diabetes reversal in mice transplanted with 1000 IEQ of syngeneic islets was not observed for islets transplanted alone while engineered matrices resulted in a diabetes median reversal time (MDRT) of 38 days. In the EFP site the MDRT with 250 IEQ of syngeneic islets within the engineered matrices was 24 days versus 86 days for islets transplanted alone. Improved function of engineered grafts was associated with enhanced and earlier (by day 7) angiogenesis. Our findings show that by engineering the transplant site to promote prompt re vascularization engraftment and long term function of islet grafts can be improved in relevant extrahepatic sites. This article is protected by copyright. All rights reserved. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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