Kin Tatsuya, Senior Peter, O'Gorman Doug, Richer Brad, Salam Abdul, Shapiro Andrew Mark James
Clinical Islet Transplant Program, University of Alberta and Capital Health, Edmonton, AB, Canada.
Transpl Int. 2008 Nov;21(11):1029-35. doi: 10.1111/j.1432-2277.2008.00719.x. Epub 2008 Jun 18.
Culturing islets can add great flexibility to a clinical islet transplant program. However, a reduction in the islet mass has been frequently observed during culture and its degree varies. The aim of this study was to identify the risk factors associated with a significant islet loss during culture. One-hundred and four islet preparations cultured in an attempt to use for transplantation constituted this study. After culture for 20 h (median), islet yield significantly decreased from 363 309 +/- 12 647 to 313 035 +/- 10 862 islet equivalent yield (IE) (mean +/- SE), accompanied by a reduction in packed tissue volume from 3.9 +/- 0.1 to 3.0 +/- 0.1 ml and islet index (IE/islet particle count) from 1.20 +/- 0.04 to 1.05 +/- 0.04. Culture did not markedly alter islet purity or percent of trapped islet. Morphology score and viability were significantly improved after culture. Of 104 islet preparations, 37 suffered a substantial islet loss (> 20%) over culture. Factors significantly associated with risk of islet loss identified by univariate analysis were longer cold ischemia time, two-layer method (TLM) preservation, lower islet purity, and higher islet index. Multivariate analysis revealed that independent predictors of islet loss were higher islet index and the use of TLM. This study provides novel information on the link between donor- isolation factors and islet loss during culture.
培养胰岛可为临床胰岛移植项目增添极大的灵活性。然而,在培养过程中经常观察到胰岛质量有所下降,且其下降程度各不相同。本研究的目的是确定与培养过程中胰岛显著丢失相关的风险因素。本研究纳入了104份为用于移植而进行培养的胰岛制剂。培养20小时(中位数)后,胰岛产量从363309±12647胰岛当量产量(IE)显著降至313035±10862(平均值±标准误),同时填充组织体积从3.9±0.1毫升降至3.0±0.1毫升,胰岛指数(IE/胰岛颗粒计数)从1.20±0.04降至1.05±0.04。培养并未显著改变胰岛纯度或被困胰岛的百分比。培养后形态学评分和活力显著改善。在104份胰岛制剂中,37份在培养过程中胰岛大量丢失(>20%)。单因素分析确定的与胰岛丢失风险显著相关的因素为较长的冷缺血时间、双层法(TLM)保存、较低的胰岛纯度和较高的胰岛指数。多因素分析显示,胰岛丢失的独立预测因素为较高的胰岛指数和TLM的使用。本研究提供了关于供体分离因素与培养过程中胰岛丢失之间联系的新信息。