The use of intrapleural pancreatic islet transplantation to enhance islet

Pancreatic islet cell transplantation provides a profound treatment for diabetic patients – improved health by avoidance of acute and chronic complications of diabetes, without the need for continued insulin injections. Yet, this treatment often requires multiple transplants due to poor islet survival and function, secondary to the suboptimal transplant tissue environment. In the setting of islet cells administered intravenously, there is a strong inflammatory response to the islets, resulting in decreased viability. In alternate transplantation sites, such as subcutaneous or intraperitoneal, the islets require passive diffusion of oxygen and nutrients from surrounding tissues for survival. Because of the limited oxygen concentration at these sites, islet viability is, again, dramatically decreased. To overcome these issues of oxygenation, recent technologies, e.g. BetaO2, utilize an external device with the significant downside of being cumbersome and requiring daily upkeep. An optimal strategy would be in vivo placement of islets in a well oxygenated environment that allows for survival and function. The work proposed in this application looks to address the issue of poor islet survival by determining the feasibility of intrapleural islet transplantation. The higher oxygen concentration and the greater surface area in the intrapleural space has the potential to provide a superior environment for the growth, survival, and function of the islet cells. Preliminary work in a murine system demonstrates the ability to place viable, functional islets in the pleural space, but the scalability of this procedure is yet to be determined. Therefore, we will investigate using the intrapleural approach to transplant islets to non-human primates, functioning as a preclinical model closely resembling human disease and physiology. The development of an optimal islet cell transplantation system in non-human primates will pave the way for more robust experimentation and in depth investigations of the physiologic and immunologic determinates of islet cell transplantation success and aid in transferring such technology to human patients.