2013 - CTS 2013 Congress

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Oral Communications 2

6.5 - Chimeric engineered bio-organ for beta cell replacement in type 1 diabetes

Presenter: Antonio, Citro, Milano, Italy
Authors: Antonio Citro1,2, Andrea Peloso1,2, Valeria Sordi1,2, Jacopo Ferrario1,2, Marcello Maestri1,2, Lorenzo Piemonti1,2

Chimeric engineered bio-organ for beta cell replacement in type 1 diabetes

Antonio Citro1,2, Andrea Peloso1,2, Valeria Sordi1,2, Jacopo Ferrario1,2, Marcello Maestri1,2, Lorenzo Piemonti1,2

1Beta Cell Biology Unit, Diabetes Research Institute-DRI, San Raffaele Scientific Institute, Milano, Italy; 2Dept. I, General Surgery , IRCCS Policlinico San Matteo, Pavia, Italy


Background. β cell replacement in type 1 diabetes can be achieved by isolated pancreatic islet transplantation. The lack of engraftment is a major limitation to a broad application in diabetic patients. In fact ~50% of the transplanted islets die shortly after transplantation. Decellularization of organs is an innovative approach in tissue engineering,it provides an acellular 3D biologic scaffold that can be re-endothelialized and seeded with selected cell population (chimeric bio-organ).
Aim:to generate a chimeric bio-organ composed of decellularized kidney seeded with pancreatic islets for beta cell function replacement in diabetic animal models. The hypothesis is that ex vivo controlled infusion and re-cellularization with pancreatic islets could improve engraftment and promote islet survival in the recipient limiting the negative events related to direct islet infusion in the liver.
Methods. Rat kidney was explanted preserving the vascular access to allow whole organ perfusion decellularization. A model of rat renal scaffold (bio-scaffold) was set up by a quick process of decellularization based on continuousperfusion with Triton X-100 0.1% and Sodium Dodecyl Sulphate–SDS- 0.1%for 4 hours. Once established the decellularization procedure, 4 bio-scaffolds were analyzed: 1 was formalin-fixed and evaluated for residual cell material by haematoxylin/eosin (HE) and DAPI staining; 1 was transplanted in recipient rats to test surgical feasibility and organ reperfusion; 1 was infused with pancreatic islets and the last one with single cell suspension of the same islet preparation after trypsin digestion. Decellularized kidney seeded with islets or dispersed islet cells was formalin-fixed after infusion and analyzed for islet cell engraftment by HE and insulin staining.
Results.The decellularization protocol has been optimized to repeatedly produce scaffolds without cellular material. Bio-scaffold structures retained the intricate vascular networks, showed preserved cortical ECM microstructure and no evidence of residual nuclei or intact cells. Syngeneic orthotopic transplantation of decellularized rat kidney showed mechanical resistance to blood flow pressure and functional perfusion. Delivery of beta cells (islets or dispersed islet cells) through arterial pathway was feasible and did not alter organ structure; cell flow was maintained along decellularized vascular network and islet cells spread in the kidney parenchyma and preferentially localized at the level of the glomeruli.
Conclusions. Our data in rat show that i) acellular whole kidney scaffolds can be obtained by perfusion decellularization; ii) decellularized kidney maintains matrix architecture and vasculature after re-implant in a syngeneic recipient; iii) decellularized kidney can be seeded with pancreatic islets after renal artery cannulation.Experiments are on going to re-endothelialize the bio-scaffold before islet infusion. Chimeric bio-organ obtained with this approach will likely normalize glycemia in diabetic animal models.

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