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Human iPSCs as Model Systems for BMP-Related Rare Diseases
Disturbances in bone morphogenetic protein (BMP) signalling contribute to onset and development of a number of rare genetic diseases, including Fibrodysplasia ossificans progressiva (FOP), Pulmonary arterial hypertension (PAH), and Hereditary haemorrhagic telangiectasia (HHT). After decades of anima...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487005/ https://www.ncbi.nlm.nih.gov/pubmed/37681932 http://dx.doi.org/10.3390/cells12172200 |
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author | Sánchez-Duffhues, Gonzalo Hiepen, Christian |
author_facet | Sánchez-Duffhues, Gonzalo Hiepen, Christian |
author_sort | Sánchez-Duffhues, Gonzalo |
collection | PubMed |
description | Disturbances in bone morphogenetic protein (BMP) signalling contribute to onset and development of a number of rare genetic diseases, including Fibrodysplasia ossificans progressiva (FOP), Pulmonary arterial hypertension (PAH), and Hereditary haemorrhagic telangiectasia (HHT). After decades of animal research to build a solid foundation in understanding the underlying molecular mechanisms, the progressive implementation of iPSC-based patient-derived models will improve drug development by addressing drug efficacy, specificity, and toxicity in a complex humanized environment. We will review the current state of literature on iPSC-derived model systems in this field, with special emphasis on the access to patient source material and the complications that may come with it. Given the essential role of BMPs during embryonic development and stem cell differentiation, gain- or loss-of-function mutations in the BMP signalling pathway may compromise iPSC generation, maintenance, and differentiation procedures. This review highlights the need for careful optimization of the protocols used. Finally, we will discuss recent developments towards complex in vitro culture models aiming to resemble specific tissue microenvironments with multi-faceted cellular inputs, such as cell mechanics and ECM together with organoids, organ-on-chip, and microfluidic technologies. |
format | Online Article Text |
id | pubmed-10487005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104870052023-09-09 Human iPSCs as Model Systems for BMP-Related Rare Diseases Sánchez-Duffhues, Gonzalo Hiepen, Christian Cells Review Disturbances in bone morphogenetic protein (BMP) signalling contribute to onset and development of a number of rare genetic diseases, including Fibrodysplasia ossificans progressiva (FOP), Pulmonary arterial hypertension (PAH), and Hereditary haemorrhagic telangiectasia (HHT). After decades of animal research to build a solid foundation in understanding the underlying molecular mechanisms, the progressive implementation of iPSC-based patient-derived models will improve drug development by addressing drug efficacy, specificity, and toxicity in a complex humanized environment. We will review the current state of literature on iPSC-derived model systems in this field, with special emphasis on the access to patient source material and the complications that may come with it. Given the essential role of BMPs during embryonic development and stem cell differentiation, gain- or loss-of-function mutations in the BMP signalling pathway may compromise iPSC generation, maintenance, and differentiation procedures. This review highlights the need for careful optimization of the protocols used. Finally, we will discuss recent developments towards complex in vitro culture models aiming to resemble specific tissue microenvironments with multi-faceted cellular inputs, such as cell mechanics and ECM together with organoids, organ-on-chip, and microfluidic technologies. MDPI 2023-09-02 /pmc/articles/PMC10487005/ /pubmed/37681932 http://dx.doi.org/10.3390/cells12172200 Text en © 2023 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 Sánchez-Duffhues, Gonzalo Hiepen, Christian Human iPSCs as Model Systems for BMP-Related Rare Diseases |
title | Human iPSCs as Model Systems for BMP-Related Rare Diseases |
title_full | Human iPSCs as Model Systems for BMP-Related Rare Diseases |
title_fullStr | Human iPSCs as Model Systems for BMP-Related Rare Diseases |
title_full_unstemmed | Human iPSCs as Model Systems for BMP-Related Rare Diseases |
title_short | Human iPSCs as Model Systems for BMP-Related Rare Diseases |
title_sort | human ipscs as model systems for bmp-related rare diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487005/ https://www.ncbi.nlm.nih.gov/pubmed/37681932 http://dx.doi.org/10.3390/cells12172200 |
work_keys_str_mv | AT sanchezduffhuesgonzalo humanipscsasmodelsystemsforbmprelatedrarediseases AT hiepenchristian humanipscsasmodelsystemsforbmprelatedrarediseases |