Bioengineering of liver assist devices.
Bioengineering of liver assist devices.
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DOI：
10.1007/s005340200095
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Toner, Mehmet
中科院分区：
文献类型：
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作者：
Tilles, Arno W;Berthiaume, Francois;Toner, Mehmet
在美国，每年有超过3万名患者死于肝衰竭。暴发性肝衰竭是一种与高死亡率相关的临床综合征，对于支持治疗无效的患者，原位肝移植是主要的治疗选择。然而，供体器官的持续稀缺限制了这种治疗方式，导致等待供体肝脏的患者死亡人数持续增加。体外生物人工肝装置可以为肝功能衰竭患者提供至关重要的支持，直到找到供体肝脏或直到患者自己的肝脏再生。尽管目前尚不清楚这种装置必须提供哪些肝脏特异性功能才能有效，但获得稳定、分化良好、功能正常的肝细胞是一个持续的挑战，可以在高细胞密度下培养。目前正在进行临床试验的许多设备受到设计的限制，这些设计容易受到底物限制，导致肝细胞功能受损。在避免底物限制的设备中，可以优化肝细胞功能，从而提高设备效率。在这篇综述中，作者描述了涉及生物人工肝发育的关键问题，并讨论了他们在带有内膜氧合器的微通道平板生物人工肝装置背景下肝细胞培养优化的经验。
Over 30 000 patients die annually in the United States from liver failure. In fulminant hepatic failure, a clinical syndrome associated with high mortality, orthotopic liver transplantation is the primary therapeutic option for patients not responding to supportive therapy. However, the persistent scarcity of donor organs has limited this therapeutic modality, resulting in a continued increase in the number of patients who die waiting for a donor liver. An extracorporeal bioartificial liver device could provide vital support to a liver failure patient until a donor liver was available or until the patient's own liver regenerated. Although it is unclear which liver-specific functions must be provided by such a device to be effective, a constant challenge has been to obtain stable, well-differentiated, and normally functioning hepatocytes that can be cultured at high cell densities. Many of the devices currently undergoing clinical trials are limited by designs which are prone to substrate limitations, resulting in compromised hepatocyte function. In devices that avoid substrate limitations, hepatocyte functions can be optimized, thereby leading to increased device efficiency. In this overview, the authors describe the critical issues involved in bioartificial liver development and discuss their experiences in hepatocyte culture optimization within the context of a microchannel, flat-plate bioartificial liver device with an internal membrane oxygenator.