Matrigel 3D bioprinting of contractile human skeletal muscle models recapitulating exercise and pharmacological responses.

Autor: Alave Reyes-Furrer A; Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland., De Andrade S; Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland.; 3D Tissues and Biofabrication, Institute of Chemistry and Biotechnology (ICBT), Zurich University of Applied Sciences, Waedenswil, Switzerland., Bachmann D; Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland., Jeker H; Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland., Steinmann M; Analytical Sciences & Imaging, Novartis Institutes for BioMedical Research, Basel, Switzerland., Accart N; Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland., Dunbar A; Analytical Sciences & Imaging, Novartis Institutes for BioMedical Research, Basel, Switzerland., Rausch M; Analytical Sciences & Imaging, Novartis Institutes for BioMedical Research, Basel, Switzerland., Bono E; 3D Tissues and Biofabrication, Institute of Chemistry and Biotechnology (ICBT), Zurich University of Applied Sciences, Waedenswil, Switzerland.; Competence Center TEDD, Institute of Chemistry and Biotechnology (ICBT), Zurich University of Applied Sciences, Waedenswil, Switzerland., Rimann M; 3D Tissues and Biofabrication, Institute of Chemistry and Biotechnology (ICBT), Zurich University of Applied Sciences, Waedenswil, Switzerland. markus.rimann@zhaw.ch.; Competence Center TEDD, Institute of Chemistry and Biotechnology (ICBT), Zurich University of Applied Sciences, Waedenswil, Switzerland. markus.rimann@zhaw.ch., Keller H; Musculoskeletal Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland. hansjoerg.keller@novartis.com.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2021 Oct 14; Vol. 4 (1), pp. 1183. Date of Electronic Publication: 2021 Oct 14.
DOI: 10.1038/s42003-021-02691-0
Abstrakt: A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering of 3D human skeletal muscle models in microplates and functional compound screening to address the lack of muscle wasting disease medication. To this end, we adapted our recently described 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Mini skeletal muscle models develop within a week exhibiting contractile, striated myofibers aligned between two attachment posts. As an in vitro exercise model, repeated high impact stimulation of contractions for 3 h by a custom-made electrical pulse stimulation (EPS) system for 24-well plates induced interleukin-6 myokine expression and Akt hypertrophy pathway activation. Furthermore, the known muscle stimulators caffeine and Tirasemtiv acutely increase EPS-induced contractile force of the models. This validated new human muscle MPS will benefit development of drugs against muscle wasting diseases. Moreover, our Matrigel 3D bioprinting platform will allow engineering of non-self-organizing complex human 3D MPS.
(© 2021. The Author(s).)
Databáze: MEDLINE
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