PDF(Pubmed)
Abstract：
Evaluating the quality of isolated human islets before transplantation is crucial for predicting the success in treating Type 1 diabetes. The current gold standard involves time-intensive in vivo transplantation into diabetic immunodeficient mice. Given the susceptibility of isolated islets to hypoxia, we hypothesized that hypoxia present in islets before transplantation could indicate compromised islet quality, potentially leading to unfavorable outcomes. To test this hypothesis, we analyzed expression of 39 hypoxia-related genes in human islets from 85 deceased donors. We correlated gene expression profiles with transplantation outcomes in 327 diabetic mice, each receiving 1200 islet equivalents grafted into the kidney capsule. Transplantation outcome was post-transplant glycemic control based on area under the curve of blood glucose over 4 weeks. In linear regression analysis, DDIT4 (R = 0.4971, P < 0.0001), SLC2A8 (R = 0.3531, P = 0.0009) and HK1 (R = 0.3444, P = 0.0012) had the highest correlation with transplantation outcome. A multiple regression model of 11 genes increased the correlation (R = 0.6117, P < 0.0001). We conclude that assessing pre-transplant hypoxia in human islets via gene expression analysis is a rapid, viable alternative to conventional in vivo assessments. This approach also underscores the importance of mitigating pre-transplant hypoxia in isolated islets to improve the success rate of islet transplantation.
摘要：
在移植前评估分离的人胰岛的质量对于预测治疗1型糖尿病的成功至关重要。当前的金标准涉及时间密集的体内移植到糖尿病免疫缺陷小鼠中。鉴于离体胰岛对缺氧的敏感性,我们假设移植前胰岛中存在缺氧可能表明胰岛质量受损，可能导致不利的结果。为了检验这个假设，我们分析了85名已故捐献者的39个缺氧相关基因在胰岛中的表达。我们将327只糖尿病小鼠的基因表达谱与移植结果相关联，每个接收1200个胰岛当量移植到肾包膜中。移植结果是基于4周内血糖曲线下面积的移植后血糖控制。在线性回归分析中，DDIT4(R=0.4971,P<0.0001),SLC2A8（R=0.3531，P=0.0009）和HK1（R=0.3444，P=0.0012）与移植结局的相关性最高。11个基因的多元回归模型增加了相关性（R=0.6117，P<0.0001）。我们得出的结论是，通过基因表达分析评估人胰岛移植前缺氧是一种快速，可行的替代常规体内评估。这种方法还强调了减轻离体胰岛移植前缺氧以提高胰岛移植成功率的重要性。
