Document Detail


A new enzyme mixture to increase the yield and transplant rate of autologous and allogeneic human islet products.
MedLine Citation:
PMID:  22318245     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The optimal enzyme blend that maximizes human islet yield for transplantation remains to be determined. In this study, we evaluated eight different enzyme combinations (ECs) in an attempt to improve islet yield. The ECs consisted of purified, intact or truncated class 1 (C1) and class 2 (C2) collagenases from Clostridium histolyticum (Ch), and neutral protease (NP) from Bacillus thermoproteolyticus rokko (thermolysin) or Ch (ChNP).
METHODS: We report the results of 249 human islet isolations, including 99 deceased donors (research n=57, clinical n=42) and 150 chronic pancreatitis pancreases. We prepared a new enzyme mixture (NEM) composed of intact C1 and C2 collagenases and ChNP in place of thermolysin. The NEM was first tested in split pancreas (n=5) experiments and then used for islet autologous (n=21) and allogeneic transplantation (n=10). Islet isolation outcomes from eight different ECs were statistically compared using multivariate analysis.
RESULTS: The NEM consistently achieved higher islet yields from pancreatitis (P<0.003) and deceased donor pancreases (P<0.001) than other standard ECs. Using the NEM, islet products met release criteria for transplantation from 8 of 10 consecutive pancreases, averaging 6510 ± 2150 islet equivalent number/gram (IEQ/g) pancreas and 694,681 ± 147,356 total IEQ/transplantation. In autologous isolation, the NEM yielded more than 200,000 IEQ from 19 of 21 pancreases (averaging 422,893 ± 181,329 total IEQ and 5979 ± 1469 IEQ/kg recipient body weight) regardless of the severity of fibrosis.
CONCLUSIONS: A NEM composed of ChNP with CIzyme high intact C1 collagenase recovers higher islet yield from deceased and pancreatitis pancreases while retaining islet quality and function.
Authors:
A N Balamurugan; Gopalakrishnan Loganathan; Melena D Bellin; Joshua J Wilhelm; James Harmon; Takayuki Anazawa; Sajjad M Soltani; David M Radosevich; Takeshi Yuasa; Mukesh Tiwari; Klearchos K Papas; Robert McCarthy; David E R Sutherland; Bernhard J Hering
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  93     ISSN:  1534-6080     ISO Abbreviation:  Transplantation     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-27     Completed Date:  2012-05-11     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  693-702     Citation Subset:  IM    
Affiliation:
Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN 55455, USA. bala@umn.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Bacillaceae / enzymology*
Chi-Square Distribution
Clostridium histolyticum / enzymology*
Endopeptidases / isolation & purification,  metabolism*
Female
Humans
Islets of Langerhans / metabolism*
Islets of Langerhans Transplantation*
Male
Microbial Collagenase / isolation & purification,  metabolism*
Middle Aged
Minnesota
Multivariate Analysis
Regression Analysis
Thermolysin / isolation & purification,  metabolism*
Tissue Survival
Tissue and Organ Harvesting / methods*
Transplantation, Autologous
Transplantation, Homologous
Treatment Outcome
Young Adult
Grant Support
ID/Acronym/Agency:
AI-065193/AI/NIAID NIH HHS; K23 DK084315/DK/NIDDK NIH HHS; R01 DK056963/DK/NIDDK NIH HHS; R01 DK056963-06/DK/NIDDK NIH HHS; R01 DK56963/DK/NIDDK NIH HHS; U01 AI065193/AI/NIAID NIH HHS; U01 AI065193-05/AI/NIAID NIH HHS; U42 RR016598/RR/NCRR NIH HHS; U42 RR016598-08/RR/NCRR NIH HHS; U42 RR16598/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
EC 3.4.-/Endopeptidases; EC 3.4.24.27/Thermolysin; EC 3.4.24.3/Microbial Collagenase
Comments/Corrections

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