TY - JOUR AU - Green, Michael L. AU - Dwulet, Francis E. AU - McCarthy, Robert PY - 2018 DA - 2018/11/07 TI - Evolution of Enzyme Requirements for Human Islet Isolation JO - OBM Transplantation SP - 024 VL - 02 IS - 04 AB - Islet transplantation is becoming an established treatment option for managing a subset of adult patients who have type 1 diabetes mellitus. The success of this procedure is dependent upon the recovery of a sufficient number of functional human islets from donor organs for subsequent transplant. Here, the use of optimized bacterial collagenase-neutral enzyme mixtures has been shown to affect the yield and quality (defined by viability and glucose-stimulated insulin secretion) of islets recovered from human pancreata. However, few reports provide a systematic approach to correlate the biochemical characteristics or dose of collagenases and proteases to the recovery of functional islets. The focus of this review is to close this gap. The review summarizes five key advances toward an understanding of how Clostridium histolyticum collagenase and bacterial neutral proteases support the release of islets from human pancreata and key collagenase biochemical characteristics that lead to higher human islet yields. This information provides a foundation to develop a model of enzymatic tissue dissociation that can serve as a guide in assessing the effectiveness of collagenase or neutral protease enzymes used for human islet isolation. One key conclusion is the importance of excess amounts of collagen degradation activity in the islet isolation procedure to ensure effective degradation of native collagen. If achieved, the selection and dose of neutral protease become the primary factors that determine the maximal release of islets from tissue. Maximal collagen degradation activity is achieved when an appropriate dose of C. histolyticum collagenase products containing primarily intact class I and class II collagenase are used in the isolation procedure. The review concludes by presenting future directions for research to develop new insights into enzymatic tissue dissociation with the goal of improving the robustness of the islet isolation process. SN - 2577-5820 UR - https://doi.org/10.21926/obm.transplant.1804024 DO - 10.21926/obm.transplant.1804024 ID - Green2018 ER -