2013 - IXA 2013 Congress


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Early Morning Workshop 3: Strategies for Overcoming Xenograft Loss

36.4 - Encapsulation combined with costimulatory blockade for preventing rejection of islet xenografts

Presenter: Collin, Weber, Blacksburg, United States
Authors:

The goals of our research are to develop� safe and effective methods to promote the long-term functional survival of islet grafts in patients with Type 1 diabetes.� We have focused our studies on donor islet immuno-isolation, using alginate microcapsules.� Although the concept is not new, the availability of highly purified reagents and recently improved protocols for microcapsule generation have yielded promising results in both small animal models and in non-human primates.� We have found that microencapsulation protects most murine islet allografts for > 1 year, without the need of host immunosuppression.� This suggests that preventing cell contact between host immune cells and donor islets is sufficient to prevent allo-islet destruction.� Similar results were found with encapsulated NOD islets in diabetic NOD recipients. Thus, encapsulation inhibits auto-immune damage to donor islets as well.� We have extensive experience with a variety of encapsulated xeno-islets (porcine, rabbit, tilapia, non-human primate, human, rodent) transplanted in diabetic NOD and NODScid recipients.� The biologic function of encapsulated these xeno-islets is remarkably normal in vivo.� However, immuno-isolation alone is not sufficient to prevent the rejection of xeno-islets in our microcapsules.� If recipients are treated with selective immuno-modulatory agents such as co-stimulatory blockade, most encapsulated porcine xeno-islet grafts function for > 1 year in NODs.� Thus, immuno-suppression and donor islet immuno-isolation are synergistic in prolong the functional survival of islet xenografts in NODs.� We have begun to test these concepts in diabetic non-human primates; and we have obtained only 1 � 2 months of partial graft function to date.� Host immune cellular� and cytokine responses have been limited, and our current microcapsules prevent the entry of IgG.� Thus, other mechanisms is donor islet injury must be involved; and these are the studies we are about to commence.�


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