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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...

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Detalles Bibliográficos
Autores principales: Sánchez-Duffhues, Gonzalo, Hiepen, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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
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