Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory.
Hepatic tissue engineering: from transplantation to customized cell-based liver directed therapies from the laboratory.
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肝组织工程：从移植到实验室定制的基于细胞的肝脏定向疗法。
DOI：
10.1111/j.1582-4934.2007.00162.x
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发表时间：
2008-01
影响因子：
5.3
通讯作者：
Kneser U
中科院分区：
文献类型：
--
作者：
Fiegel HC;Kaufmann PM;Bruns H;Kluth D;Horch RE;Vacanti JP;Kneser U
今天，肝移植仍然是治疗终末期肝病引起的肝功能衰竭的唯一方法。供体器官短缺、成本高以及需要免疫抑制药物仍然是肝移植领域的主要限制因素。因此，替代的创新的基于细胞的肝脏定向治疗，例如肝组织工程，正在研究中，目的是在未来可以创造出人工肝组织，并用于替代患者的肝功能。在这种情况下使用细胞代替器官应该允许(i)在体外阶段扩增细胞，（ii）对用于移植的细胞进行遗传或免疫学操作，（iii）在细胞库中进行组织分型和低温保存，以及（iv）在重新植入之前对患者自身细胞进行体外遗传修饰。肝细胞的功能和分化受三维器官结构的影响。聚合物基质的使用允许新组织的三维形成和基质表面的适当修饰的特异性刺激，这可能是移植细胞适当分化的必要条件。此外，在三维基质上培养肝细胞允许在流动生物反应器系统中培养，提高了培养细胞的功能和存活率。基于生物反应器技术，开发出体外肝支持生物人工肝装置（BAL）。虽然BALs改善了临床和代谢状况，但提高了患者的生存率尚未得到证实。对于体内肝脏置换，将组织工程技术结合三维高多孔基质和细胞移植的概念可能是有用的。在这样的概念下，全肝块移植、长期植入和功能以及动物模型代谢缺陷的纠正可以通过一个基本可逆的过程来实现。未来的研究必须调查哪种环境条件和移植系统最适合人工功能肝组织的发展，包括在临床环境中潜在使用的血液供应。
Today, liver transplantation is still the only curative treatment for liver failure due to end-stage liver diseases. Donor organ shortage, high cost and the need of immunosuppressive medications are still the major limitations in the field of liver transplantation. Thus, alternative innovative cell-based liver directed therapies, for example, liver tissue engineering, are under investigation with the aim that in future an artificial liver tissue could be created and be used for the replacement of the liver function in patients. Using cells instead of organs in this setting should permit (i) expansion of cells in an in vitro phase, (ii) genetic or immunological manipulation of cells for transplantation, (iii) tissue typing and cryopreservation in a cell bank and (iv) the ex vivo genetic modification of patient's own cells prior to re-implantation. Function and differentiation of liver cells are influenced by the three-dimensional organ architecture. The use of polymeric matrices permits the three-dimensional formation of a neo tissue and specific stimulation by adequate modification of the matrix surface, which might be essential for appropriate differentiation of transplanted cells. In addition, culturing hepatocytes on three-dimensional matrices permits culture in a flow bioreactor system with increased function and survival of the cultured cells. Based on bioreactor technology, bioartificial liver devices (BAL) are developed for extracorporeal liver support. Although BALs improved clinical and metabolic conditions, increased patient survival rates have not been proven yet. For intracorporeal liver replacement, a concept that combines tissue engineering using three-dimensional, highly porous matrices with cell transplantation could be useful. In such a concept, whole liver mass transplantation, long-term engraftment and function as well as correction of a metabolic defect in animal models could be achieved with a principally reversible procedure. Future studies have to investigate which environmental conditions and transplantation system would be most suitable for the development of artificial functional liver tissue including blood supply for a potential use in a clinical setting.
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影响因子：
6.2
作者：
GILBERT, JC;TAKADA, T;VACANTI, JP
通讯作者：
VACANTI, JP
影响因子：
3.3
作者：
JOHNSON, LB;AIKEN, J;VACANTI, JP
通讯作者：
VACANTI, JP
影响因子：
4.8
作者：
Berthiaume, F;Moghe, PV;Yarmush, ML
通讯作者：
Yarmush, ML
影响因子：
--
作者：
Fidkowski, C;Kaazempur-Mofrad, MR;Wang, YD
通讯作者：
Wang, YD
影响因子：
3.7
作者：
GUGUENGUILLOUZO, C;CLEMENT, B;GUILLOUZO, A
通讯作者：
GUILLOUZO, A