4 years ago

Beneficial effect of recombinant rC1rC2 collagenases on human islet function: Efficacy of low dose enzymes on pancreas digestion and yield

Michael L. Green, William W. Tucker, Appakalai N Balamurugan, Subhashree Venugopal, Michael G. Hughes, SriPrakash Mokshagundam, Gopalakrishnan Loganathan, Siddharth Narayanan, Francis E. Dwulet, Stuart K. Williams, Maheswaran Dhanasekaran, Andrew G. Breite, Robert C. McCarthy
High number of human islets can be isolated using modern purified tissue dissociation enzymes, however it requires using >20 Wunsch Unit (WU)/gram of pancreas for digestion. Attempts to reduce this dose have resulted in pancreas under-digestion and poor islet recovery but improved islet function. In this study, we achieved high number of functional islets using low dose of recombinant collagenase enzyme mixture (RCEM). The collagenase dose used in these isolations is about 42% of the natural collagenase enzyme mixture (NCEM) dose commonly used to digest a 100g pancreas. Low dose RCEM was efficient in digesting entire pancreases to obtain higher yield (5,535±830 IEQ/gram and 2,582±925 IEQ/gram, P<0.05) and lesser undigested tissue (16.7±5% and 37.8±3%, P<0.05) when compared to low dose NCEM (12WU/gram). Additionally, low dose RCEM islets retained better morphology (confirmed by scanning electron microscopy), and higher in vitro basal insulin release (2391 ± 1342 μU/ml and 1778 ± 978 μU/ml; P<0.05) when compared to standard NCEM dose. Nude mouse bioassay demonstrated better islet function for low dose RCEM (AUC 24,968) over low (AUC-38,225) or standard NCEM dose (AUC-38,685), p<0.05. This is the first report indicating that islet function can be improved by using low dose rC1rC2 (RCEM). This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/ajt.14542

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.