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Inventing Engineered Organoids for end-stage liver failure patients
Journal of Molecular Histology ( IF 2.9 ) Pub Date : 2022-07-27 , DOI: 10.1007/s10735-022-10085-7
Radiana D Antarianto 1, 2 , Amer Mahmood 3 , Angela Giselvania 3, 4 , Ayu Aa Prima Asri Dewi 5, 6 , Jatmiko Gustinanda 7 , Jeanne Adiwinata Pawitan 1, 2, 8, 9
Affiliation  

End-stage liver disease (ESLD) is a term used clinically in reference to a group of liver diseases with liver transplantation as the choice of treatment. Due to the limitations of liver transplantation, alternative treatments are needed. The use of primary human hepatocytes represents a valid alternative treatment, but the limitations related to hepatocyte quality, viability, function, conservation, and storage need to be overcome. Transplanted hepatocytes have only been followed for 6–9 months. Therefore, long-term causes of failures are not yet established, including rejection, apoptosis, or other causes. Other alternative therapies to replace liver transplantation include plasmapheresis, hemodiafiltration, and artificial livers. Unfortunately, these methods are highly limited due to availability, high cost, anaphylaxis reaction, development-deposition of immune-complexes, and restricted functionality. Liver organoids, which utilize stem cells instead of ‘impractical’ adult hepatocytes, may be a solution for the development of a complex bioartificial liver. Recent studies have explored the benefits of differentiating mature hepatocytes from stem cells inside a bioreactor. When the use of human-induced Hepatocytes (hiHeps) was investigated in mouse and pig models of liver failure, liver failure markers were decreased, hepatocyte function indicated by albumin synthesis improved, and survival time increased. Bioartificial liver treatment may decrease the infiltration of inflammatory cells into liver tissue by down-regulating pro-inflammatory cytokines.



中文翻译:

为终末期肝衰竭患者发明工程类器官

终末期肝病(ESLD)是临床上使用的术语,指以肝移植为治疗选择的一组肝病。由于肝移植的局限性,需要替代治疗。使用原代人肝细胞代表了一种有效的替代治疗方法,但需要克服与肝细胞质量、活力、功能、保存和储存相关的限制。移植的肝细胞仅被跟踪了 6-9 个月。因此,尚未确定失败的长期原因,包括排斥、细胞凋亡或其他原因。替代肝移植的其他替代疗法包括血浆置换术、血液透析滤过和人工肝。不幸的是,这些方法由于可用性、高成本、过敏反应、免疫复合物的发育沉积和功能受限。利用干细胞代替“不切实际的”成体肝细胞的肝类器官可能是开发复杂生物人工肝的一种解决方案。最近的研究探索了将成熟肝细胞与生物反应器内的干细胞区分开来的好处。当在小鼠和猪肝衰竭模型中研究人诱导肝细胞 (hiHeps) 的使用时,肝衰竭标志物减少,白蛋白合成指示的肝细胞功能得到改善,存活时间增加。生物人工肝治疗可以通过下调促炎细胞因子来减少炎症细胞向肝组织的浸润。利用干细胞而不是“不切实际的”成体肝细胞,可能是开发复杂生物人工肝的解决方案。最近的研究探索了将成熟肝细胞与生物反应器内的干细胞区分开来的好处。当在小鼠和猪肝衰竭模型中研究人诱导肝细胞 (hiHeps) 的使用时,肝衰竭标志物减少,白蛋白合成指示的肝细胞功能得到改善,存活时间增加。生物人工肝治疗可以通过下调促炎细胞因子来减少炎症细胞向肝组织的浸润。利用干细胞而不是“不切实际的”成体肝细胞,可能是开发复杂生物人工肝的解决方案。最近的研究探索了将成熟肝细胞与生物反应器内的干细胞区分开来的好处。当在小鼠和猪肝衰竭模型中研究人诱导肝细胞 (hiHeps) 的使用时,肝衰竭标志物减少,白蛋白合成指示的肝细胞功能得到改善,存活时间增加。生物人工肝治疗可以通过下调促炎细胞因子来减少炎症细胞向肝组织的浸润。当在小鼠和猪肝衰竭模型中研究人诱导肝细胞 (hiHeps) 的使用时,肝衰竭标志物减少,白蛋白合成指示的肝细胞功能得到改善,存活时间增加。生物人工肝治疗可以通过下调促炎细胞因子来减少炎症细胞向肝组织的浸润。当在小鼠和猪肝衰竭模型中研究人诱导肝细胞 (hiHeps) 的使用时,肝衰竭标志物减少,白蛋白合成指示的肝细胞功能得到改善,存活时间增加。生物人工肝治疗可以通过下调促炎细胞因子来减少炎症细胞向肝组织的浸润。

更新日期:2022-07-28
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