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人类青少年胰岛用于临床的适用性。

Suitability of human juvenile pancreatic islets for clinical use.

作者信息

Balamurugan A N, Chang Y, Bertera S, Sands A, Shankar V, Trucco M, Bottino R

机构信息

Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Diabetologia. 2006 Aug;49(8):1845-54. doi: 10.1007/s00125-006-0318-0. Epub 2006 Jun 17.

DOI:10.1007/s00125-006-0318-0
PMID:16783471
Abstract

AIMS/HYPOTHESIS: The limited availability of deceased donor pancreases suitable for pancreas and islet transplantation calls for a broader utilisation of donor tissue for transplantation purposes. Young donors, representing, fortunately, a minor but significant pool of individuals, have been largely under-employed, mainly because of anatomical and functional incompatibilities with potential recipients. For islet transplantation, the isolation of pancreatic islets from young donors rarely occurs, because of technical problems. As a result of the peculiar characteristics of young donor pancreases, the standard isolation procedure does not allow efficient separation of the islets from the surrounding exocrine tissue, and favours the generation of mantled islets. Nonetheless, young donor islets offer high qualitative and clinically appealing characteristics.

SUBJECTS AND METHODS

We standardised a modified methodology to obtain purified and mantle-free human islets from young donors. This method principally involves efficient delivery of isolation enzyme with reduced mechanical disruption of the pancreas combined with additional filtration steps.

RESULTS

We were able to obtain purified and mantle-free human islets from donors as young as 6 months of age with good morphological and functional properties. The good qualitative characteristics of the islets, evidenced in vitro, were proven in vivo, as they were qualitatively superior to islets of older donors in transplantation studies.

CONCLUSIONS/INTERPRETATION: This study justifies the utilisation of islets derived from young donors for islet transplantation.

摘要

目的/假设:适合胰腺和胰岛移植的已故供体胰腺供应有限,这就需要更广泛地利用供体组织用于移植目的。年轻供体幸运地代表了一小部分但很重要的个体群体,在很大程度上未得到充分利用,主要是因为其在解剖结构和功能上与潜在受体不匹配。对于胰岛移植,由于技术问题,很少从年轻供体中分离胰岛。由于年轻供体胰腺的特殊特征,标准分离程序无法有效地将胰岛与周围的外分泌组织分离,并且有利于形成被膜胰岛。尽管如此,年轻供体的胰岛具有高质量和临床上吸引人的特征。

对象与方法

我们标准化了一种改良方法,以从年轻供体中获得纯化且无被膜的人胰岛。该方法主要包括有效地输送分离酶,同时减少对胰腺的机械破坏,并结合额外的过滤步骤。

结果

我们能够从年仅6个月大的供体中获得具有良好形态和功能特性的纯化且无被膜的人胰岛。胰岛在体外显示出的良好质量特性在体内也得到了证实,因为在移植研究中,它们在质量上优于年长供体的胰岛。

结论/解读:本研究证明了利用年轻供体的胰岛进行胰岛移植是合理的。

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本文引用的文献

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Facilitating physiologic self-regeneration: a step beyond islet cell replacement.促进生理自我再生:超越胰岛细胞替代的一步。
Pharm Res. 2006 Feb;23(2):227-42. doi: 10.1007/s11095-005-9095-6. Epub 2006 Jan 1.
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Harmful delayed effects of exogenous isolation enzymes on isolated human islets: relevance to clinical transplantation.
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Five-year follow-up after clinical islet transplantation.临床胰岛移植后的五年随访。
胰岛移植的未来已来。
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Enzyme Development for Human Islet Isolation: Five Decades of Progress or Stagnation?用于人类胰岛分离的酶的发展:五十年的进步还是停滞?
Rev Diabet Stud. 2017 Spring;14(1):22-38. doi: 10.1900/RDS.2017.14.22. Epub 2017 Jun 12.
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Fluorogenic Peptide Substrate for Quantification of Bacterial Enzyme Activities.用于定量细菌酶活性的荧光肽底物。
Sci Rep. 2017 Mar 13;7:44321. doi: 10.1038/srep44321.
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Total Pancreatectomy With Islet Autotransplantation Resolves Pain in Young Children With Severe Chronic Pancreatitis.全胰切除术联合胰岛自体移植可缓解重度慢性胰腺炎患儿的疼痛。
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Dynamics and Regulation of Insulin Secretion in Pancreatic Islets from Normal Young Children.正常幼儿胰岛中胰岛素分泌的动力学与调节
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Single-Cell Transcriptomics of the Human Endocrine Pancreas.人类内分泌胰腺的单细胞转录组学
Diabetes. 2016 Oct;65(10):3028-38. doi: 10.2337/db16-0405. Epub 2016 Jun 30.
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Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion.1型糖尿病中的致病性CD4 T细胞识别由肽融合形成的表位。
Science. 2016 Feb 12;351(6274):711-4. doi: 10.1126/science.aad2791.
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