Characterization of collagenase blend enzymes for human islet transplantation

Transplantation. 2007 Dec 27;84(12):1568-75. doi: 10.1097/01.tp.0000295719.88525.60.

Abstract

Background: Efficient islet isolation represents a necessary requirement for successful islet transplantation as a treatment for type 1 diabetes. The choice of collagenase for pancreas digestion is critical for the isolation outcome, and Liberase is the most widely used enzyme, although large intra-batched variability in activity and efficiency has been observed.

Methods: The aim of this study was to characterize Liberase components and their relative role in pancreas digestion. Liberase batches were characterized by microelectrophoresis.

Results: By means of microelectrophoresis, we identified three main proteins each with different prevalences between batches. Two proteins were found to correspond to class I (CI) and one to class II (CII) collagenase. In a series of 163 islet isolations, we observed that the CII correlated with islet yield (P<0.001) and digestion time (P<0.001); additionally, CI directly correlated with purity (P=0.028). Finally, when CII and one of the CI isoforms were >50 percentile, 15 of 36 preparations were transplanted, with 27 of 127 transplanted in the other cases (P=0.013).

Conclusion: These results represent an important step toward the characterization of enzymes, with the final aim of identifying key components for a standardized product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Separation / methods
  • Collagenases / analysis
  • Collagenases / metabolism
  • Collagenases / therapeutic use*
  • Humans
  • Islets of Langerhans / cytology*
  • Islets of Langerhans Transplantation / methods*
  • Pancreas / cytology
  • Thermolysin / analysis
  • Thermolysin / metabolism
  • Thermolysin / therapeutic use*

Substances

  • Collagenases
  • Liberase
  • Thermolysin