Vishwakarma Sandeep Kumar, Bardia Avinash, Lakkireddy Chandrakala, Nagarapu Raju, Habeeb Md Aejaz, Khan Aleem Ahmed
Central Laboratory for Stem Cell Research and Translational Medicine, Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Hyderabad 500058, Telangana, India.
World J Hepatol. 2018 Jan 27;10(1):22-33. doi: 10.4254/wjh.v10.i1.22.
To develop appropriate humanized three-dimensional model system for drug testing.
Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses.
The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available and models for identifying cellular and molecular dynamics of pharmacological drugs.
The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.
开发适用于药物测试的人性化三维模型系统。
在本研究中，利用人肝干细胞在脱细胞肝支架内重新填充构建生物工程化人源化肝脏，该支架模拟天然器官的解剖结构和生理功能。使用六种细胞色素P - 450探针来有效鉴定生物工程化人源化肝脏中的药物代谢。对生物工程化肝脏中的药物代谢研究进行评估，以确定吸收、分布、代谢、排泄和毒性反应。
生物工程化人源化肝脏表现出人类肝脏的细胞和分子特征。生物工程化肝脏呈现出具有完整血管系统和细胞外基质的三维天然结构。人肝细胞的植入类似于人类肝脏。药物代谢研究为识别药理药物的细胞和分子动力学提供了一个合适的平台，可替代现有的模型。
本研究为开发适用于药理测试的人性化临床前模型系统铺平了道路。这种方法可能会降低临床前药物测试的成本和时间，并进一步克服异种系统中的解剖和生理差异。
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