Clostripain, the Missing Link in the Enzyme Blend for Efficient Human Islet Isolation.

Area of Science:

• Biotechnology
• Transplantation Immunology
• Endocrinology

Background:

• Effective digestive enzymes are critical for successful islet isolation.
• Supplemental proteases synergize with collagenase for pancreas digestion.
• Tryptic-like activity is linked to efficient enzyme blends.

Purpose of the Study:

• To evaluate if adding clostripain, an enzyme with tryptic-like activity, improves islet isolation efficacy.
• To assess the impact of clostripain on pancreas digestion and islet yield.
• To determine if clostripain enhances the rate of isolations meeting transplantation criteria.

Main Methods:

• Clostripain was added to the enzyme blend prior to pancreas perfusion.
• Islet isolation followed standard procedures, with rigorous evaluation of isolation parameters and islet quality.
• Control organs were matched to clostripain-treated organs based on key donor and logistical factors.

Main Results:

• No significant differences were observed in pancreas weight, dissection, digestion, or harvest times between groups.
• Glucose-stimulated insulin release was comparable between control and clostripain groups.
• Clostripain-processed pancreases showed improved total islet equivalents, purified tissue volume, and higher rates of meeting transplantation criteria.

Conclusions:

• Clostripain addition to the enzyme blend significantly enhanced islet yields and transplantation rates.
• Clostripain facilitated gentle pancreas digestion and maintained islet functionality.
• The use of clostripain in enzyme blends has been integrated into standard islet isolation protocols at major centers.