Rescue purification maximizes the use of human islet preparations for transplantation
Rescue purification maximizes the use of human islet preparations for transplantation
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DOI：
10.1111/j.1600-6143.2005.00698.x
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发表时间：
2005-01-01
影响因子：
8.8
通讯作者：
Ricordi, C
中科院分区：
文献类型：
--
作者：
Ichii, H;Pileggi, A;Ricordi, C
胰岛纯化过程的相对低效可能妨碍获得足够的胰岛用于移植，即使具有足够的纯化前计数。在这项研究中，我们确定了额外的纯化步骤对总胰岛产量和胰腺利用率的影响，在我们的center. Twenty五个胰腺进行了处理，使用自动化的方法，然后连续梯度纯化（CGP），和纯度较低的胰岛馏分进行额外的救援梯度纯化（RGP）。将CGP和RGP胰岛联合移植到1型糖尿病患者体内，CGP和RGP胰岛移植到化学性糖尿病小鼠体内，细胞活力、体外胰岛素分泌和功能无明显差异。RGP对最终制剂的平均贡献为27.9 +/-19.9%。在25个制备物中的12个中，CGP产生< 5000 IEQkg的受体体重，并且将RGP胰岛包含到最终制备物中允许获得移植所需的最小胰岛数量。移植的胰岛导致持续的C肽产生，HbA 1（C）正常化和胰岛素非依赖性或减少胰岛素需求。RGP可能有助于最大限度地增加成功用于移植方案的胰岛制剂的数量。
The relative inefficiency of the islet purification process may hamper obtaining enough islets for transplantation even with adequate pre-purification counts. In this study, we determined the effect of an additional purification step on total islet yields and pancreas utilization at our center.Twenty-five pancreata were processed using the automated method followed by continuous gradient purification (CGP), and the less pure islet fractions were subjected to additional rescue gradient purification (RGP). CGP and RGP islets were combined and transplanted into patients with type 1 diabetes.CGP and RGP islets showed no significant differences in cell viability, insulin secretion in vitro and function when transplanted into chemically diabetic mice. Mean RGP contribution to the final preparation was 27.9 +/- 19.9%. In 12 of 25 preparations, CGP yielded < 5000 IEQkg of recipient body weight, and inclusion of RGP islets to the final preparation allowed to obtain the minimal islet number required for transplantation. Transplanted islets resulted in sustained C-peptide production, HbA1(C) normalization and insulin-independence or reduced insulin requirements.Taken together, our data suggest that RGP islets are comparable in terms of viability and potency to CGP islets. RGP may be of assistance in maximizing the number of islet preparations successfully used in transplant protocols.