A novel preservation solution containing a JNK inhibitory peptide efficiently improves islet yield for porcine islet isolation.
A novel preservation solution containing a JNK inhibitory peptide efficiently improves islet yield for porcine islet isolation.
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含有 JNK 抑制肽的新型保存液可有效提高猪胰岛分离的胰岛产量。
DOI：
10.1097/tp.0000000000002555
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Watanabe M
中科院分区：
文献类型：
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作者：
Noguchi H;Miyagi-Shiohira C;Nakashima Y;Ebi N;Hamada E;Tamaki Y;Kuwae K;Kitamura S;Kobayashi N;Saitoh I;Watanabe M
背景对于胰岛移植，威斯康星州大学（UW）溶液中的胰腺保存与缺点相关，例如胶原酶抑制，导致胰岛产量低和胰岛活性差。在这项研究中，我们评估了一种新的保存液，细胞外型c-Jun N-末端激酶（JNK）的通道，包含（EJ）solution.MethodsThe EJ解决方案具有高钠低钾的组合物与低粘度相比，UW解决方案。此外，EJ解决方案包含一个最近开发的JNK抑制剂从我们的实验室。ResultsWe第一次比较EJ解决方案与UW解决方案的性能。EJ组纯化前后胰岛产量显著高于UW组。其次，我们比较了EJ溶液与不含JNK抑制剂的EJ溶液（EJ-J溶液）的性能。胰腺保存在EJ液中后，JNK活性在胰岛分离过程中维持在相对较低的水平。EJ组纯化前后的胰岛产量明显高于EJ-J组。将胰岛移植到链脲佐菌素诱导的糖尿病小鼠中后，EJ和EJ-J组分别有61.5%和7.7%的糖尿病小鼠血糖水平达到正常血糖范围。此外，EJ解决方案表现出减少抑制胶原酶消化相比，UW solution.ConclusionsAdvantages EJ解决方案UW解决方案是抑制JNK活性和减少胶原酶抑制。因此，EJ溶液可能比UW溶液更适合于胰岛分离。
BackgroundFor islet transplantation, pancreas preservation in University of Wisconsin (UW) solution is associated with disadvantages, such as collagenase inhibition, resulting in poor islet yield and islets with poor viability. In this study, we evaluated a novel preservation solution, the extracellular-type c-Jun N-terminal kinase (JNK) inhibitor-containing (EJ) solution.MethodsThe EJ solution has high sodium-low potassium composition with low viscosity compared to UW solution. Moreover, EJ solution contains a recently developed JNK inhibitor from our laboratory.ResultsWe first compared the performance of EJ solution with that of UW solution. Islet yield before and after purification was significantly higher in the EJ group than in the UW group. Second, we compared the performance of EJ solution with that of EJ solution without the JNK inhibitor (EJ-J solution). After pancreas preservation in EJ solution, JNK activity was maintained at a relatively low level during islet isolation. Islet yield before and after purification was significantly higher in the EJ group than in the EJ-J group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 61.5% and 7.7% of diabetic mice in the EJ and EJ-J groups, respectively. Moreover, EJ solution exhibited reduced inhibition of collagenase digestion compared with UW solution.ConclusionsAdvantages of EJ solution over UW solution were inhibition of JNK activity and reduced collagenase inhibition. EJ solution may therefore be more suitable for islet isolation than UW solution.