Assessment of Islet Quality

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): Type 1 diabetes affects more than 1 million north Americans. Transplantation of islets of Langerhans offers the promise of a cure by a simple injection into the liver. The recent report from Edmonton describing success in 15 consecutive patients has led to a multi-center trial to confirm reproducibility of these results and to worldwide interest in improving procedures. Effective quality assessment methods are needed to ensure safety and in vivo efficacy. Because insufficient viable islet volume or excessive damaged tissue may lead to failure, tools for reproducible quantitative evaluation of meaningful properties in islet preparations are prerequisites for consistent success of islet transplants, for improvements in islet isolation, and for the conduct of islet transplantation research. The development of such tools is needed because currently used methods are inadequate and not predictive of clinical outcome. This project is based on a central hypothesis: Accurate knowledge of islet quality prior to transplantation will be predictive of in vivo efficacy in the absence of immune rejection. Islet quality can be assessed quantitatively in both pure and impure preparations in terms of viable islet volume and the relative amounts of viable and dead tissue (fractional viability). Oxygen consumption rate (OCR) in conjunction with DNA measurements is the primary tool for assessing these properties. The objectives of this project are (1) to develop tools for reliable in vitro assessment of islet preparation quality prior to transplantation in terms of viable islet volume and fractional viability, (2) to systematically evaluate the predictive capability of these tools by following transplantation outcome in small animals; (3) to add these tools to existing methods to assess the quality of islet preparations for human transplantation, to generate a database of islet quality parameters, and to use it retrospectively to determine their usefulness in predicting in vivo efficacy.