scholarly journals Challenges for the Applications of Human Pluripotent Stem Cell-Derived Liver Organoids

2021 ◽  
Vol 9 ◽  
Author(s):  
Mingyang Chang ◽  
Mariia S. Bogacheva ◽  
Yan-Ru Lou
Keyword(s):  
Stem Cell ◽  
Drug Discovery ◽  
Regenerative Medicine ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cell ◽  
Hepatic Differentiation ◽  
Culture Systems ◽  
Organoid Culture ◽  
Liver Organoids

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.

Use of 3D culture systems to generate human induced pluripotent stem cell-derived [beta]-cells in vitro

2018 ◽  
Author(s):  
Fantuzzi Federica ◽  
Toivonen Sanna ◽  
Schiavo Andrea Alex ◽  
Pachera Nathalie ◽  
Rajaei Bahareh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Beta Cells ◽  
Pluripotent Stem Cell ◽  
3D Culture ◽  
Induced Pluripotent Stem Cell ◽  
Culture Systems ◽  
Induced Pluripotent

Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids

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

Development of quantitative direct prediction algorithm for the human target organ similarity of human pluripotent stem cell-derived organoids and cells

2020 ◽  
Author(s):  
Mi-Ok Lee ◽  
Sugi Lee ◽  
Cho-Rok Jung ◽  
Jea-Woon Ryu ◽  
Ye Seul Son ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Prediction Algorithm ◽  
Specific Gene ◽  
Human Pluripotent Stem Cell ◽  
High Quality ◽  
Web Based ◽  
Human Organs ◽  
Differentiated Cells

Abstract Human pluripotent stem cell (hPSC)-derived organoids and differentiated cells have similar characteristics, such as cell types, structure, and functions, to human organs and tissues. Thus, in vitro human organoids and tissue-specific cells serve as a superior alternative to conventional cell lines and animal models in drug development and regenerative medicine. However, since hPSC-derived organoids and differentiated cells show fetal-like features, further differentiation and maturation methods have been developed for the generation of high-quality in vitro models of the corresponding human organs and tissues. Therefore, for a simple and reproducible analysis of the quality of organoids and cells to compensate for the shortcomings of existing experimental validation studies, a quantitative evaluation method should be developed. In this study, using the GTEx database (a total of 8,555 samples in 53 tissues), we constructed a quantitative calculation system (organ-specific panels and calculation algorithm) to assess the similarity to the human lung, stomach, and heart and confirmed the algorithm using in-house RNA-seq data (total RNA from 20 tissues). To evaluate our system, we generated hPSC-derived lung organoids, gastric organoids, and cardiomyocytes and detected 33.4%, 51.7%, and 83.4% similarity, respectively, to the corresponding human target organs. To facilitate access and use of our system for researchers, we developed the web-based user interface (Web-based Similarity Analysis System, W-SAS; for liver, lung, stomach, and heart) presenting similarity to the appropriate organs as percentages and specific gene expression patterns. Thus, the W-SAS system could provide valuable information for the generation of high-quality and readily available organoids/cells differentiated from hPSCs and a strategy to guide proper lineage-oriented differentiation.

scholarly journals Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tanja Hyvärinen ◽  
Anu Hyysalo ◽  
Fikret Emre Kapucu ◽  
Laura Aarnos ◽  
Andrey Vinogradov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Microelectrode Array ◽  
Functional Characterization ◽  
Principal Component ◽  
Network Activity ◽  
Human Pluripotent Stem Cell ◽  
Cortical Networks ◽  
Cortical Cultures

AbstractHuman pluripotent stem cell (hPSC)-derived neurons provide exciting opportunities for in vitro modeling of neurological diseases and for advancing drug development and neurotoxicological studies. However, generating electrophysiologically mature neuronal networks from hPSCs has been challenging. Here, we report the differentiation of functionally active hPSC-derived cortical networks on defined laminin-521 substrate. We apply microelectrode array (MEA) measurements to assess network events and compare the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures. In both of these networks, activity developed through a similar sequence of stages and time frames; however, the hPSC-derived networks showed unique patterns of bursting activity. The hPSC-derived networks developed synchronous activity, which involved glutamatergic and GABAergic inputs, recapitulating the classical cortical activity also observed in rodent counterparts. Principal component analysis (PCA) based on spike rates, network synchronization and burst features revealed the segregation of hPSC-derived and rat network recordings into different clusters, reflecting the species-specific and maturation state differences between the two networks. Overall, hPSC-derived neural cultures produced with a defined protocol generate cortical type network activity, which validates their applicability as a human-specific model for pharmacological studies and modeling network dysfunctions.

Functional maturation of human pluripotent stem cell derived cardiomyocytes in vitro – Correlation between contraction force and electrophysiology

Biomaterials ◽  
2015 ◽  
Vol 51 ◽  
pp. 138-150 ◽  
Author(s):  
Marcelo C. Ribeiro ◽  
Leon G. Tertoolen ◽  
Juan A. Guadix ◽  
Milena Bellin ◽  
Georgios Kosmidis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Human Pluripotent Stem Cell ◽  
Contraction Force ◽  
Functional Maturation
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