scholarly journals Human Pluripotent Stem Cell Applications in Drug Discovery and Toxicology – An overview

Author(s):  
Shiva Prasad Potta ◽  
Tomo Šarić ◽  
Michael Heke ◽  
Harinath Bahudhanapati ◽  
Jürgen Hescheler
2016 ◽  
Vol 15 (11) ◽  
pp. 1455-1458 ◽  
Author(s):  
Yimu Zhao ◽  
Anastasia Korolj ◽  
Nicole Feric ◽  
Milica Radisic

Author(s):  
Juan Huang ◽  
Qi Feng ◽  
Li Wang ◽  
Bingying Zhou

Cardiac diseases are the leading cause of deaths worldwide; however, to date, there has been limited progress in the development of therapeutic options for these conditions. Animal models have been the most extensively studied methods to recapitulate a wide variety of cardiac diseases, but these models exhibit species-specific differences in physiology, metabolism and genetics, which lead to inaccurate and unpredictable drug safety and efficacy results, resulting in drug attrition. The development of human pluripotent stem cell (hPSC) technology in theory guarantees an unlimited source of human cardiac cells. These hPSC-derived cells are not only well suited for traditional two-dimensional (2-D) monoculture, but also applicable to more complex systems, such as three-dimensional (3-D) organoids, tissue engineering and heart on-a-chip. In this review, we discuss the application of hPSCs in heart disease modeling, cell therapy, and next-generation drug discovery. While the hPSC-related technologies still require optimization, their advances hold promise for revolutionizing cell-based therapies and drug discovery.


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.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3290
Author(s):  
Alexandra Benchoua ◽  
Marie Lasbareilles ◽  
Johana Tournois

One of the major obstacles to the identification of therapeutic interventions for central nervous system disorders has been the difficulty in studying the step-by-step progression of diseases in neuronal networks that are amenable to drug screening. Recent advances in the field of human pluripotent stem cell (PSC) biology offers the capability to create patient-specific human neurons with defined clinical profiles using reprogramming technology, which provides unprecedented opportunities for both the investigation of pathogenic mechanisms of brain disorders and the discovery of novel therapeutic strategies via drug screening. Many examples not only of the creation of human pluripotent stem cells as models of monogenic neurological disorders, but also of more challenging cases of complex multifactorial disorders now exist. Here, we review the state-of-the art brain cell types obtainable from PSCs and amenable to compound-screening formats. We then provide examples illustrating how these models contribute to the definition of new molecular or functional targets for drug discovery and to the design of novel pharmacological approaches for rare genetic disorders, as well as frequent neurodegenerative diseases and psychiatric disorders.


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