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O'Gorman D.,Clinical Islet Transplant Program | Kin T.,Clinical Islet Transplant Program | Imes S.,Clinical Islet Transplant Program | Pawlick R.,University of Alberta | And 2 more authors.
Transplantation | Year: 2010

Background: After the discontinuation of the manufacturing Liberase HI because of a small potential for prion disease transmission, Roche Diagnostics (Indianapolis, IN) developed a new enzyme product (Liberase MTF [mammalian tissue free]), which is similar to Liberase HI with the exception that no mammalian tissue is used in the manufacture of the collagenase component. We report our experience using the MTF enzyme in clinical islet isolations compared with Serva NB-1 with modified enzyme delivery method. Methods: Islets were isolated from 41 pancreata using MTF enzyme (n=17) or NB-1 enzyme (n=24). NB-1 enzymes were delivered using a modified (nonsimultaneous) enzyme delivery method whereas isolations using MTF used the standard method of simultaneous collagenase and thermolysin perfusion. Islets were purified on a COBE 2991 Cell Blood Processor and subsequently cultured. Results: The average islet mass after purification was 392±36×10 islet equivalent (IE) for MTF versus 371±40×10 IE for Serva NB-1 (P=0.63). Post-IE/cm of tissue was 110±9×10 IE/cm and 91±11×10 IE/cm for MTF and NB-1, respectively (P=0.07). The isolation success rate (>400,000 IE) for MTF was 53% compared with 33% for Serva (P=0.33). Conclusion: We conclude that MTF may be successfully used for high-yield human islet isolation and clinical transplantation and provides similar quality islets to those derived using NB-1. © 2010 by World Health Organization. Source

O'Gorman D.,Clinical Islet Transplant Program | Kin T.,Clinical Islet Transplant Program | Pawlick R.,University of Alberta | Imes S.,Clinical Islet Transplant Program | And 2 more authors.
Islets | Year: 2013

Background: Pancreas dissociation is a critical initial component of the islet isolation procedure and introduces high variability based on factors including the enzyme type, specificity and potency. Product refinement and alterations to the application strategies have improved isolation outcomes over time; however, islet utilization from donor organs remains low. In this study we evaluate a low endotoxin-high activity grade neutral protease in clinical islet isolation. Materials and Methods: The use of a non-collagenolytic enzyme, either thermolysin or high active neutral protease, was randomized in clinical islet isolations to evaluate efficacy. Additionally a retrospective comparison to neutral protease NB was conducted. Results: The thermolysin group had lower trapped islet population and increased purity and post-culture islet mass in comparison to high active grade neutral protease. Comparison of neutral protease NB GMP grade to high active neutral protease displayed no measurable difference in islet mass or viability and transplantation outcomes at 1 mo post-transplant were favorable for both groups. Conclusions: High activity neutral protease can generate clinical grade islets and may prove beneficial to islet function and viability based on a reduced endotoxin load but dosing of neutral protease requires ongoing optimization. © 2013 Landes Bioscience. Source

Schwindt S.T.,University of Alberta | Hubert G.,Clinical Islet Transplant Program | Koh A.,Clinical Islet Transplant Program | Shapiro A.M.J.,Clinical Islet Transplant Program | And 2 more authors.
Canadian Journal of Diabetes | Year: 2012

Clinical islet transplantation (CIT) has emerged as an effective therapy for type 1 diabetes mellitus. Adults undergoing CIT are at high risk for reduced bone mineral density (BMD) due to poor nutritional status, use of immunosuppressive therapy known to influence bone metabolism and ongoing refractory disease. The objective of this study was to determine the prevalence of reduced BMD in CIT recipients. A retrospective pair-matched study design was conducted in adults with type 1 diabetes pre- and post-CIT (n=18). BMD was measured using dual x-ray absorptiometry (DXA) at the femoral neck (FN), hip and spine. Overall, absolute BMD (g/cm2) did not decrease significantly between pre- and post-CIT measures (p>0.05). Routine evaluation of BMD including variables known to influence bone health (medications, lifestyle factors), is warranted in patients undergoing CIT. © 2012 Canadian Diabetes Association. Source

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