Rizwan Muhammad
Department of Biomedical Engineering, Michigan Technological University, 1400 Townsend Dr, 305 MM. Bldg., Houghton, MI, 49931, USA.
Adv Biol (Weinh). 2024 Feb;8(2):e2300450. doi: 10.1002/adbi.202300450. Epub 2023 Oct 16.
Liver tissue engineering has undergone remarkable developments since the late 20th century, transitioning from simple two-dimensional cultures to sophisticated three-dimensional organoid models for drug toxicity assessments. Stem cell innovations have enabled the creation of liver organoids for disease modelling and tissue engineering. However, a key limitation is the absence of functional bile ducts in these organoids, crucial for replicating bile-duct related diseases. Bile, synthesized by hepatocytes, plays a vital role in digesting fats and expelling lipid-soluble wastes, including drug byproducts. Diseases impeding bile flow are responsible for many liver transplants and can cause severe conditions such as liver cirrhosis, causing over 50,000 annual deaths in the US. Current liver organoids, while bile-producing, are devoid of bile ducts, limiting their efficacy in mimicking diseases related to bile flow. This article underscores the pressing need to incorporate bile ducts in engineered liver tissues, delves into the challenges faced in this effort, and highlights potential solutions through biomaterial and bioengineering techniques. Such advancements will offer researchers enhanced insights into bile duct disorders and pave the way for exploring innovative therapeutic strategies.
自20世纪末以来，肝脏组织工程取得了显著进展，从简单的二维培养发展到用于药物毒性评估的复杂三维类器官模型。干细胞创新使得创建用于疾病建模和组织工程的肝脏类器官成为可能。然而，一个关键限制是这些类器官中缺乏功能性胆管，而胆管对于复制与胆管相关的疾病至关重要。由肝细胞合成的胆汁在消化脂肪和排出脂溶性废物（包括药物副产品）方面起着至关重要的作用。阻碍胆汁流动的疾病是许多肝脏移植的原因，并且可能导致诸如肝硬化等严重病症，在美国每年造成超过50000人死亡。目前的肝脏类器官虽然能够产生胆汁，但缺乏胆管，限制了它们在模拟与胆汁流动相关疾病方面的功效。本文强调了在工程化肝脏组织中纳入胆管的迫切需求，深入探讨了这一努力中面临的挑战，并通过生物材料和生物工程技术突出了潜在的解决方案。这些进展将为研究人员提供对胆管疾病的更深入见解，并为探索创新治疗策略铺平道路。
