Functional skeletal muscle constructs from transdifferentiated human fibroblasts

Abstract Transdifferentiation of human non-muscle cells directly into myogenic cells by forced expression of MyoD represents one route to obtain highly desirable human myogenic cells. However, functional properties of the tissue constructs derived from these transdifferentiated cells have been rarel...

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Autores principales:	Bin Xu, Allison Siehr, Wei Shen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/19ce38e9d34a4b1a83dadebdafcd9c10
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spelling	oai:doaj.org-article:19ce38e9d34a4b1a83dadebdafcd9c102021-12-02T12:03:15ZFunctional skeletal muscle constructs from transdifferentiated human fibroblasts10.1038/s41598-020-78987-82045-2322https://doaj.org/article/19ce38e9d34a4b1a83dadebdafcd9c102020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78987-8https://doaj.org/toc/2045-2322Abstract Transdifferentiation of human non-muscle cells directly into myogenic cells by forced expression of MyoD represents one route to obtain highly desirable human myogenic cells. However, functional properties of the tissue constructs derived from these transdifferentiated cells have been rarely studied. Here, we report that three-dimensional (3D) tissue constructs engineered with iMyoD-hTERT-NHDFs, normal human dermal fibroblasts transduced with genes encoding human telomerase reverse transcriptase and doxycycline-inducible MyoD, generate detectable contractile forces in response to electrical stimuli upon MyoD expression. Withdrawal of doxycycline in the middle of 3D culture results in 3.05 and 2.28 times increases in twitch and tetanic forces, respectively, suggesting that temporally-controlled MyoD expression benefits functional myogenic differentiation of transdifferentiated myoblast-like cells. Treatment with CHIR99021, a Wnt activator, and DAPT, a Notch inhibitor, leads to further enhanced contractile forces. The ability of these abundant and potentially patient-specific and disease-specific cells to develop into functional skeletal muscle constructs makes them highly valuable for many applications, such as disease modeling.Bin XuAllison SiehrWei ShenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bin Xu Allison Siehr Wei Shen Functional skeletal muscle constructs from transdifferentiated human fibroblasts
description	Abstract Transdifferentiation of human non-muscle cells directly into myogenic cells by forced expression of MyoD represents one route to obtain highly desirable human myogenic cells. However, functional properties of the tissue constructs derived from these transdifferentiated cells have been rarely studied. Here, we report that three-dimensional (3D) tissue constructs engineered with iMyoD-hTERT-NHDFs, normal human dermal fibroblasts transduced with genes encoding human telomerase reverse transcriptase and doxycycline-inducible MyoD, generate detectable contractile forces in response to electrical stimuli upon MyoD expression. Withdrawal of doxycycline in the middle of 3D culture results in 3.05 and 2.28 times increases in twitch and tetanic forces, respectively, suggesting that temporally-controlled MyoD expression benefits functional myogenic differentiation of transdifferentiated myoblast-like cells. Treatment with CHIR99021, a Wnt activator, and DAPT, a Notch inhibitor, leads to further enhanced contractile forces. The ability of these abundant and potentially patient-specific and disease-specific cells to develop into functional skeletal muscle constructs makes them highly valuable for many applications, such as disease modeling.
format	article
author	Bin Xu Allison Siehr Wei Shen
author_facet	Bin Xu Allison Siehr Wei Shen
author_sort	Bin Xu
title	Functional skeletal muscle constructs from transdifferentiated human fibroblasts
title_short	Functional skeletal muscle constructs from transdifferentiated human fibroblasts
title_full	Functional skeletal muscle constructs from transdifferentiated human fibroblasts
title_fullStr	Functional skeletal muscle constructs from transdifferentiated human fibroblasts
title_full_unstemmed	Functional skeletal muscle constructs from transdifferentiated human fibroblasts
title_sort	functional skeletal muscle constructs from transdifferentiated human fibroblasts
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/19ce38e9d34a4b1a83dadebdafcd9c10
work_keys_str_mv	AT binxu functionalskeletalmuscleconstructsfromtransdifferentiatedhumanfibroblasts AT allisonsiehr functionalskeletalmuscleconstructsfromtransdifferentiatedhumanfibroblasts AT weishen functionalskeletalmuscleconstructsfromtransdifferentiatedhumanfibroblasts
_version_	1718394734115815424

Functional skeletal muscle constructs from transdifferentiated human fibroblasts

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