Cargando…

Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery

The pharmaceutical industry is in high need of efficient and relevant in vitro liver models, which can be incorporated in their drug discovery pipelines to identify potential drugs and their toxicity profiles. Current liver models often rely on cancer cell lines or primary cells, which both have maj...

Descripción completa

Detalles Bibliográficos
Autores principales: Tricot, Tine, Verfaillie, Catherine M., Kumar, Manoj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834601/
https://www.ncbi.nlm.nih.gov/pubmed/35159250
http://dx.doi.org/10.3390/cells11030442
_version_ 1784649226954735616
author Tricot, Tine
Verfaillie, Catherine M.
Kumar, Manoj
author_facet Tricot, Tine
Verfaillie, Catherine M.
Kumar, Manoj
author_sort Tricot, Tine
collection PubMed
description The pharmaceutical industry is in high need of efficient and relevant in vitro liver models, which can be incorporated in their drug discovery pipelines to identify potential drugs and their toxicity profiles. Current liver models often rely on cancer cell lines or primary cells, which both have major limitations. However, the development of human induced pluripotent stem cells (hiPSCs) has created a new opportunity for liver disease modeling, drug discovery and liver toxicity research. hiPSCs can be differentiated to any cell of interest, which makes them good candidates for disease modeling and drug discovery. Moreover, hiPSCs, unlike primary cells, can be easily genome-edited, allowing the creation of reporter lines or isogenic controls for patient-derived hiPSCs. Unfortunately, even though liver progeny from hiPSCs has characteristics similar to their in vivo counterparts, the differentiation of iPSCs to fully mature progeny remains highly challenging and is a major obstacle for the full exploitation of these models by pharmaceutical industries. In this review, we discuss current liver-cell differentiation protocols and in vitro iPSC-based liver models that could be used for disease modeling and drug discovery. Furthermore, we will discuss the challenges that still need to be overcome to allow for the successful implementation of these models into pharmaceutical drug discovery platforms.
format Online
Article
Text
id pubmed-8834601
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88346012022-02-12 Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery Tricot, Tine Verfaillie, Catherine M. Kumar, Manoj Cells Review The pharmaceutical industry is in high need of efficient and relevant in vitro liver models, which can be incorporated in their drug discovery pipelines to identify potential drugs and their toxicity profiles. Current liver models often rely on cancer cell lines or primary cells, which both have major limitations. However, the development of human induced pluripotent stem cells (hiPSCs) has created a new opportunity for liver disease modeling, drug discovery and liver toxicity research. hiPSCs can be differentiated to any cell of interest, which makes them good candidates for disease modeling and drug discovery. Moreover, hiPSCs, unlike primary cells, can be easily genome-edited, allowing the creation of reporter lines or isogenic controls for patient-derived hiPSCs. Unfortunately, even though liver progeny from hiPSCs has characteristics similar to their in vivo counterparts, the differentiation of iPSCs to fully mature progeny remains highly challenging and is a major obstacle for the full exploitation of these models by pharmaceutical industries. In this review, we discuss current liver-cell differentiation protocols and in vitro iPSC-based liver models that could be used for disease modeling and drug discovery. Furthermore, we will discuss the challenges that still need to be overcome to allow for the successful implementation of these models into pharmaceutical drug discovery platforms. MDPI 2022-01-27 /pmc/articles/PMC8834601/ /pubmed/35159250 http://dx.doi.org/10.3390/cells11030442 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tricot, Tine
Verfaillie, Catherine M.
Kumar, Manoj
Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery
title Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery
title_full Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery
title_fullStr Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery
title_full_unstemmed Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery
title_short Current Status and Challenges of Human Induced Pluripotent Stem Cell-Derived Liver Models in Drug Discovery
title_sort current status and challenges of human induced pluripotent stem cell-derived liver models in drug discovery
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834601/
https://www.ncbi.nlm.nih.gov/pubmed/35159250
http://dx.doi.org/10.3390/cells11030442
work_keys_str_mv AT tricottine currentstatusandchallengesofhumaninducedpluripotentstemcellderivedlivermodelsindrugdiscovery
AT verfailliecatherinem currentstatusandchallengesofhumaninducedpluripotentstemcellderivedlivermodelsindrugdiscovery
AT kumarmanoj currentstatusandchallengesofhumaninducedpluripotentstemcellderivedlivermodelsindrugdiscovery