scholarly journals Peer Review #1 of "Generation of human liver organoids from pluripotent stem cell-derived hepatic endoderms (v0.1)"

2019 ◽  
Vol 71 (5) ◽  
pp. 970-985 ◽  
Author(s):  
Seon Ju Mun ◽  
Jae-Sung Ryu ◽  
Mi-Ok Lee ◽  
Ye Seul Son ◽  
Soo Jin Oh ◽  
...  

2019 ◽  
Vol 244 (8) ◽  
pp. 702-708
Author(s):  
Pooja Chaudhari ◽  
Lipeng Tian ◽  
Zhaohui Ye ◽  
Yoon-Young Jang

Pharmaceutical drug development and clinical testing is associated with billions of dollars, and often the time and money spent does not result in a viable drug formulation. The pharmaceutical industry has long relied on animal models for testing efficacy, toxicity and specificity of novel drugs. However, the studies cannot be fully relied upon, as animal models are not reflective of human pathophysiology and drug response, which results in drugs being pulled from development as late as at stage IV, after billions of dollars have already been invested in such an effort. With the advent of adult-induced pluripotent stem cell technology, came an era which offered the potential of pursing human relevant developmental and pathogenesis research and drug testing on patient-induced pluripotent stem cell-derived differentiated cells, consciously reflecting human responses with regard to drug safety, toxicity, efficacy, and side effects. Specifically, human-induced pluripotent stem cell-derived hepatobiliary cells and tissues may be a more human-relevant model system to address the biggest barrier to drug safety and approval: hepatotoxicity. In this review, we address the potential of human-induced pluripotent stem cell-based hepatobiliary differentiation technology as a means to study human liver development and hepatic cell fate determination, and to model liver diseases in an effort to develop a new human-relevant preclinical platform for drug development. Impact statement In this review, we address the potential of human-induced pluripotent stem cell-based hepatobiliary differentiation technology as a means to study human liver development and cell fate determination, and to model liver diseases in an effort to develop a new human-relevant preclinical platform for drug development.


Author(s):  
Mingyang Chang ◽  
Mariia S. Bogacheva ◽  
Yan-Ru Lou

The current organoid culture systems allow pluripotent and adult stem cells to self-organize to form three-dimensional (3D) structures that provide a faithful recapitulation of the architecture and function of in vivo organs. In particular, human pluripotent stem cell-derived liver organoids (PSC-LOs) can be used in regenerative medicine and preclinical applications, such as disease modeling and drug discovery. New bioengineering tools, such as microfluidics, biomaterial scaffolds, and 3D bioprinting, are combined with organoid technologies to increase the efficiency of hepatic differentiation and enhance the functional maturity of human PSC-LOs by precise control of cellular microenvironment. Long-term stabilization of hepatocellular functions of in vitro liver organoids requires the combination of hepatic endodermal, endothelial, and mesenchymal cells. To improve the biological function and scalability of human PSC-LOs, bioengineering methods have been used to identify diverse and zonal hepatocyte populations in liver organoids for capturing heterogeneous pathologies. Therefore, constructing engineered liver organoids generated from human PSCs will be an extremely versatile tool in in vitro disease models and regenerative medicine in future. In this review, we aim to discuss the recent advances in bioengineering technologies in liver organoid culture systems that provide a timely and necessary study to model disease pathology and support drug discovery in vitro and to generate cell therapy products for transplantation.


Sign in / Sign up

Export Citation Format

Share Document