Mauriello Romanazzi, Giuseppe (2010) Innovative strategies to improve islet transplatation. Doctoral Thesis.
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In spite of the great promise of pancreatic islet transplantation in the clinical management of type 1 diabetes, several technical problems related to the transplated tissue's viability have yet to be solved before the technique can be used as a routine therapeutic tool. The aim of this work is to explore new strategies to improve pancreatic islet transplantation, exploiting combined cell and gene therapy approaches.
We have established optimized lentiviral-mediated gene transfer protocols into islet beta cells and endothelial progenitors, the two cellular components playing a major role in determining engraftment efficiency and ultimately clinical benefit for the patient. Both islets and endothelial progenitor cells could be efficiently transduced by lentiviral vectors carrying expression cassettes for the green fluorescent protein (GFP), used as a genetic marker.
The viability of engineered cells was documented in vitro in microchimerism experiments, where lentiviral-transduced cells were able to participate in the formation of complex structures (micro-organoids) that recapitulate the initial phases of engraftment and neovascularization in vivo.
The combination of these techniques opens the way to the enhancement of islet transplantation procedures by ex vivo approaches based on the modulation of tissue viability, host immune responses, and neovascularization of the grafted tissue.
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