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Degraded collagenase deteriorates islet viability.

H Brandhorst1, N Raemsch-Guenther, C Raemsch

  • 1Department of Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden.

Transplantation Proceedings
|April 1, 2008
PubMed
Summary

Degraded collagenase isomers negatively impact islet isolation and function. Using intact collagenase (Ci) yields better islet quality and post-transplant outcomes compared to degraded forms (Cd).

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Transplantation Science

Background:

  • Enzyme blends, including collagenase class I (CI) and II (CII), are crucial for clinical islet isolation.
  • Previous research indicates that degraded CI in enzyme lots may hinder islet release from pancreata.

Purpose of the Study:

  • To evaluate the impact of degraded collagenase isomers on islet function both in vitro and after transplantation.
  • To compare the efficacy of intact (Ci) versus degraded (Cd) collagenase in islet isolation and function.

Main Methods:

  • Collagenase was separated into intact and degraded isomers.
  • Rat islets were isolated using neutral protease and either intact (Ci) or degraded (Cd) collagenase.
  • Islet function was assessed in vitro and post-transplantation in diabetic nude mice.

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Main Results:

  • Degraded collagenase (Cd) reduced digestion time but resulted in lower islet yield and higher fragmentation compared to intact collagenase (Ci).
  • Islets isolated with Cd showed reduced viability and in vitro function.
  • Transplanted islets from Cd isolation failed to promote recipient weight gain, unlike those from Ci isolation.

Conclusions:

  • Degraded collagenase isomers significantly affect islet function after transplantation.
  • The purification process of collagenase must consider the impact of degraded isomers on islet isolation and function.