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整体器官组织工程在肝病学中的应用。

Application of whole-organ tissue engineering in hepatology.

机构信息

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children, 51 Blossom Street, Boston, MA 02114, USA.

出版信息

Nat Rev Gastroenterol Hepatol. 2012 Dec;9(12):738-44. doi: 10.1038/nrgastro.2012.140. Epub 2012 Aug 14.

DOI:10.1038/nrgastro.2012.140
PMID:22890112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3732057/
Abstract

Initially hailed as the ultimate solution to organ failure, engineering of vascularized tissues such as the liver has stalled because of the need for a well-structured circulatory system that can maintain the cells seeded inside the construct. A new approach has evolved to overcome this obstacle. Whole-organ decellularization is a method that retains most of the native vascular structures of the organ, providing microcirculatory support and structure, which can be anastomosed with the recipient circulation. The technique was first applied to the heart and then adapted for the liver. Several studies have shown that cells can be eliminated, the extracellular matrix and vasculature are reasonably preserved and, after repopulation with hepatocytes, these grafts can perform hepatic functions in vitro and in vivo. Progress is rapidly being made as researchers are addressing several key challenges to whole-organ tissue engineering, such as ensuring correct cell distribution, nonparenchymal cell seeding, blood compatibility, immunological concerns, and the source of cells and matrices.

摘要

最初,工程化血管化组织(如肝脏)被吹捧为解决器官衰竭的终极方案,但由于需要一个结构良好的循环系统来维持构建体内部的细胞,该技术的发展陷入了停滞。为了克服这一障碍,出现了一种新的方法。整个器官去细胞化是一种保留器官大部分固有血管结构的方法,为细胞提供了微循环支持和结构,这些结构可以与受体循环吻合。该技术最初应用于心脏,然后适用于肝脏。多项研究表明,可以消除细胞,合理保留细胞外基质和脉管系统,并且在用肝细胞再种植后,这些移植物可以在体外和体内发挥肝脏功能。随着研究人员解决整个器官组织工程的几个关键挑战,如确保正确的细胞分布、非实质细胞接种、血液相容性、免疫问题以及细胞和基质的来源,该技术正在迅速发展。

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本文引用的文献

1
Human-scale whole-organ bioengineering for liver transplantation: a regenerative medicine approach.人体尺度全器官生物工程用于肝移植:再生医学方法。
Cell Transplant. 2013;22(2):231-42. doi: 10.3727/096368912X654939. Epub 2012 Aug 27.
2
Design concepts and strategies for tissue engineering scaffolds.组织工程支架的设计理念与策略。
Biotechnol Appl Biochem. 2011 Nov-Dec;58(6):423-38. doi: 10.1002/bab.60. Epub 2011 Nov 27.
3
Induced anti-non gal antibodies in human xenograft recipients.诱导人类异种移植受者的抗非 Gal 抗体。
Transplantation. 2012 Jan 15;93(1):11-6. doi: 10.1097/TP.0b013e31823be870.
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Use of decellularized porcine liver for engineering humanized liver organ.使用脱细胞猪肝构建人源化肝脏器官。
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Growth factor/heparin-immobilized collagen gel system enhances viability of transplanted hepatocytes and induces angiogenesis.生长因子/肝素固定化胶原凝胶系统增强了移植肝细胞的活力并诱导了血管生成。
J Biosci Bioeng. 2011 Sep;112(3):265-72. doi: 10.1016/j.jbiosc.2011.05.003.
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Organ engineering based on decellularized matrix scaffolds.基于脱细胞基质支架的器官工程。
Trends Mol Med. 2011 Aug;17(8):424-32. doi: 10.1016/j.molmed.2011.03.005. Epub 2011 Apr 21.
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Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells.不完全的 DNA 甲基化是人类诱导多能干细胞中体细胞转录记忆的基础。
Nat Cell Biol. 2011 May;13(5):541-9. doi: 10.1038/ncb2239. Epub 2011 Apr 17.
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Decellularized liver matrix as a carrier for the transplantation of human fetal and primary hepatocytes in mice.去细胞化的肝基质作为载体在小鼠中移植人胎肝和原代肝细胞。
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Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds.整体器官组织工程:三维基质支架的脱细胞化和再细胞化。
Annu Rev Biomed Eng. 2011 Aug 15;13:27-53. doi: 10.1146/annurev-bioeng-071910-124743.
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A whole-organ regenerative medicine approach for liver replacement.整体器官再生医学方法用于肝脏替代。
Tissue Eng Part C Methods. 2011 Jun;17(6):677-86. doi: 10.1089/ten.TEC.2010.0698. Epub 2011 Apr 20.