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Effects of Genetically Modified Human Skin Fibroblasts, Stably Overexpressing Hepatocyte Growth Factor, on Hepatic Functions of Co-cultured C3A Cells.
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2020-09-03 , DOI: 10.1002/bit.27551 Agnieszka Wencel 1 , Malgorzata Ciezkowska 1 , Monika Wisniewska 1 , Karolina E Zakrzewska 1, 2 , Dorota G Pijanowska 1 , Krzysztof D Pluta 1
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2020-09-03 , DOI: 10.1002/bit.27551 Agnieszka Wencel 1 , Malgorzata Ciezkowska 1 , Monika Wisniewska 1 , Karolina E Zakrzewska 1, 2 , Dorota G Pijanowska 1 , Krzysztof D Pluta 1
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Diseases leading to terminal hepatic failure are among the most common causes of death worldwide. Transplant of the whole organ is the only effective method to cure liver failure. Unfortunately, this treatment option is not available universally due to the serious shortage of donors. Thus, alternative methods have been developed that are aimed at prolonging the life of patients, including hepatic cells transplantation and bridging therapy based on hybrid bioartificial liver devices. Parenchymal liver cells are highly differentiated and perform many complex functions, such as detoxification and protein synthesis. Unfortunately, isolated hepatocytes display a rapid decline in viability and liver‐specific functions. A number of methods have been developed to maintain hepatocytes in their highly differentiated state in vitro, amongst them the most promising being 3D growth scaffolds and decellularized tissues or coculture with other cell types required for the heterotypic cell‐cell interactions. Here we present a novel approach to the hepatic cells culture based on the feeder layer cells genetically modified using lentiviral vector to stably produce additional amounts of hepatocyte growth factor and show the positive influence of these coculture conditions on the preservation of the hepatic functions of the liver parenchymal cells' model—C3A cells.
中文翻译：
稳定过表达肝细胞生长因子的转基因人皮肤成纤维细胞对共培养 C3A 细胞肝功能的影响。
导致晚期肝功能衰竭的疾病是世界范围内最常见的死亡原因之一。全器官移植是治愈肝功能衰竭的唯一有效方法。不幸的是，由于捐赠者严重短缺，这种治疗方案并非普遍可用。因此，已经开发出旨在延长患者生命的替代方法，包括肝细胞移植和基于混合生物人工肝装置的桥接疗法。实质肝细胞高度分化并执行许多复杂的功能，例如解毒和蛋白质合成。不幸的是，分离的肝细胞的活力和肝脏特异性功能迅速下降。已经开发了许多方法来在体外维持肝细胞处于高度分化状态，其中最有前途的是 3D 生长支架和脱细胞组织，或与异型细胞间相互作用所需的其他细胞类型共培养。在这里，我们提出了一种新的肝细胞培养方法，该方法基于使用慢病毒载体进行基因改造的饲养层细胞，以稳定产生额外量的肝细胞生长因子，并显示这些共培养条件对保护肝脏肝功能的积极影响实质细胞模型——C3A 细胞。
更新日期：2020-09-03
中文翻译：
稳定过表达肝细胞生长因子的转基因人皮肤成纤维细胞对共培养 C3A 细胞肝功能的影响。
导致晚期肝功能衰竭的疾病是世界范围内最常见的死亡原因之一。全器官移植是治愈肝功能衰竭的唯一有效方法。不幸的是，由于捐赠者严重短缺，这种治疗方案并非普遍可用。因此，已经开发出旨在延长患者生命的替代方法，包括肝细胞移植和基于混合生物人工肝装置的桥接疗法。实质肝细胞高度分化并执行许多复杂的功能，例如解毒和蛋白质合成。不幸的是，分离的肝细胞的活力和肝脏特异性功能迅速下降。已经开发了许多方法来在体外维持肝细胞处于高度分化状态，其中最有前途的是 3D 生长支架和脱细胞组织，或与异型细胞间相互作用所需的其他细胞类型共培养。在这里，我们提出了一种新的肝细胞培养方法，该方法基于使用慢病毒载体进行基因改造的饲养层细胞，以稳定产生额外量的肝细胞生长因子，并显示这些共培养条件对保护肝脏肝功能的积极影响实质细胞模型——C3A 细胞。
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