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向胰岛单个供体移植的策略。

Strategies toward single-donor islets of Langerhans transplantation.

机构信息

Clinical Islet Transplant Program, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Curr Opin Organ Transplant. 2011 Dec;16(6):627-31. doi: 10.1097/MOT.0b013e32834cfb84.

DOI:10.1097/MOT.0b013e32834cfb84
PMID:22068022
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3268080/
Abstract

PURPOSE OF REVIEW

The current review addresses a critical need in clinical islet transplantation, namely the routine transition from the requirement of two to four donors down to one donor per recipient. The ability to achieve single-donor islet transplantation will provide many more islet grafts for treatment of an ever-expanding patient base with type 1 diabetes (T1DM) with poor glycemic control. Avoiding exposure of recipients to multiple different donor human leukocyte associated (HLA) antigens is critical if risk of donor sensitization is to be avoided. This point is important as further islet or pancreas transplants in the remote future or the potential future need for a solid organ kidney transplant may become prohibitive if the recipient is sensitized.

RECENT FINDINGS

This review addresses systematically all areas that contribute to the success or failure of single-donor islet engraftment, beginning with donor-related factors, optimizing islet isolation and culture conditions, and describes a series of strategies in the treatment of the recipient to prevent inflammation, apoptosis, islet thrombosis, and improve metabolic functional outcome, all of which will lead to improved single-donor engraftment success.

SUMMARY

If single-donor islet transplantation can be achieved routinely, therapy will become more widely available, more accepted by the transplant community (currently pancreas transplantation requires only a single donor), and this situation will have a major impact overall as an effective treatment option in T1DM.

摘要

目的综述

本综述针对临床胰岛移植的一个关键需求,即将每位受者需要的 2 至 4 个供者胰岛减少到 1 个供者。实现单供者胰岛移植的能力将为越来越多的 1 型糖尿病(T1DM)患者提供更多的胰岛移植物,这些患者血糖控制不佳。如果要避免供者致敏的风险,避免受者接触多种不同的供者人类白细胞相关(HLA)抗原至关重要。如果受者致敏,这一点很重要,因为在遥远的将来进一步进行胰岛或胰腺移植,或者未来潜在需要实体器官肾移植,可能会变得不可行。

最新发现

本综述系统地讨论了所有有助于单供者胰岛移植成功或失败的因素,首先是供者相关因素,然后优化胰岛分离和培养条件,并描述了一系列针对受者的治疗策略,以防止炎症、细胞凋亡、胰岛血栓形成和改善代谢功能结局,所有这些都将提高单供者胰岛移植的成功率。

总结

如果能常规实现单供者胰岛移植,治疗将更广泛应用,更被移植界接受(目前胰腺移植只需 1 个供者),这种情况将对 T1DM 的有效治疗选择产生重大影响。

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Strategies toward single-donor islets of Langerhans transplantation.向胰岛单个供体移植的策略。
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2
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4
HLA sensitization in islet transplantation.胰岛移植中的HLA致敏
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Clinical islet transplantation at the University of Alberta--the Edmonton experience.阿尔伯塔大学的临床胰岛移植——埃德蒙顿经验。
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De Novo Donor-Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes.新发供者特异性 HLA 抗体与 1 型糖尿病患者胰岛移植后移植物功能的快速丧失相关。
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本文引用的文献

1
Anti-inflammatory properties of exenatide in human pancreatic islets.人胰腺胰岛中艾塞那肽的抗炎特性。
Cell Transplant. 2012;21(4):633-48. doi: 10.3727/096368911X576027. Epub 2011 Jun 7.
2
The caspase inhibitor IDN-6556 (PF3491390) improves marginal mass engraftment after islet transplantation in mice.半胱天冬酶抑制剂 IDN-6556(PF3491390)可改善胰岛移植后边缘质量的植入。
Surgery. 2011 Jul;150(1):48-55. doi: 10.1016/j.surg.2011.02.023. Epub 2011 May 18.
3
Improving efficacy of clinical islet transplantation with iodixanol-based islet purification, thymoglobulin induction, and blockage of IL-1β and TNF-α.用碘海醇为基础的胰岛纯化、胸腺球蛋白诱导以及阻断白介素-1β和肿瘤坏死因子-α来提高临床胰岛移植的疗效。
Cell Transplant. 2011;20(10):1641-7. doi: 10.3727/096368910X564058. Epub 2011 Mar 8.
4
Changing pattern of organ donation at a single center: are potential brain dead donors being lost to donation after cardiac death?单一中心器官捐献模式的变化:潜在的脑死亡供者是否因心死亡后捐献而流失?
Am J Transplant. 2010 Nov;10(11):2536-40. doi: 10.1111/j.1600-6143.2010.03215.x.
5
Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade.在不使用钙调神经磷酸酶抑制剂的免疫抑制方案下,通过 T 细胞黏附或共刺激阻断,对 1 型糖尿病患者进行胰岛移植。
Transplantation. 2010 Dec 27;90(12):1595-601. doi: 10.1097/TP.0b013e3181fe1377.
6
Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success.经移植旁输注胰岛素-肝素可显著提高单次供者临床胰岛移植的成功率。
Transplantation. 2010 Feb 27;89(4):465-71. doi: 10.1097/TP.0b013e3181c478fd.
7
Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction.西格列汀对移植肾功能障碍胰岛移植受者的长期代谢和激素影响。
Cell Transplant. 2009;18(10):1247-59. doi: 10.3727/096368909X474456.
8
Liraglutide, a long-acting human glucagon-like peptide 1 analogue, improves human islet survival in culture.利拉鲁肽,一种长效人胰高血糖素样肽 1 类似物,可改善人胰岛在培养中的存活。
Transpl Int. 2010 Mar 1;23(3):259-65. doi: 10.1111/j.1432-2277.2009.00984.x. Epub 2009 Oct 12.
9
Porcine marginal mass islet autografts resist metabolic failure over time and are enhanced by early treatment with liraglutide.猪边缘块状胰岛自体移植可长期抵抗代谢衰竭,且早期使用利拉鲁肽治疗可增强其效果。
Endocrinology. 2009 May;150(5):2145-52. doi: 10.1210/en.2008-1116. Epub 2009 Jan 8.
10
Low molecular weight dextran sulfate is well tolerated in humans and increases endogenous expression of islet protective hepatocyte growth factor.低分子量硫酸葡聚糖在人体中耐受性良好,并可增加胰岛保护性肝细胞生长因子的内源性表达。
Transplantation. 2008 Dec 15;86(11):1523-30. doi: 10.1097/TP.0b013e3181890593.