The Choice of Enzyme for Human Pancreas Digestion is a Critical Factor for Increasing the Success of Islet Isolation.

摘要: Successful human islet isolation is essential for clinical and research applications,1-4 greatly influenced by selecting appropriate enzyme(s) pancreas digestion.5-10 Hence, developing using consistently high-quality enzymes a key element isolations. Advancements in obtaining non-good manufacturing practice liberase HI indeed made major progress to achieve successful isolation11,12 allowed an increase the number of patients receiving transplants.13 However, 2007, use isolations was ceased due safety concerns possible prion contamination from bovine tissue-derived raw materials.14 Liberase mixture collagenase neutral protease (NP) not highly purified hence, lot-to-lot variability concern failure long term storage sporadic.9,12,15 Therefore, there great demand GMP-grade, pure, low endotoxin digestion enzyme replace among specialists commercial manufacturers obtain high quality islets.6,16-18 Consequently, NB1 supplemented with NP adopted many centers globally as alternative isolation.6,19,20 Indeed, several have been transplanted islets isolated this enzyme, suggesting that may be promising product replacing HI. limitation its efficacy isolate younger donors ultimate outcome different donor populations. Furthermore, it has reported contains degraded collagenase; therefore, higher doses are required isolations.8,21 Collagenase, NP, clostripain produced Clostridium histolyticum,15 whereas thermolysin Bacillus thermoproteolyticus rokko.12 Collagenase (class I II isoforms) either Thermolysin or currently used digestion. combination CIzyme HA (containing nondegradable class [60%] [40%]) found effective isolating transplantation, but GMP products.21 mammalian tissue-free collagenase/thermolysin (MTF C/T) shown transplantation compared NB1/NP.6,22 All types aforementioned purposes. advantage particular specific supplier over another debatable often subjectively determined team's experiences.21,23 It overall NB1/NP comparable HI.5,19 In retrospective analysis, 221 pancreata 3 commercially available enzymes, HI, NB1/NP, MTF C/T were compared.