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2023_Biofabrication_Mimicking_TejederaA.pdf (2.87 MB)

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2023-09-27

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cc by (c) Tejedera Villafranca, Ainoa et al., 2023
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/202898

Mimicking sarcolemmal damage in vitro: a contractile 3D model of skeletal muscle for drug testing in Duchenne muscular dystrophy

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https://doi.org/10.1088/1758-5090/acfb3d

Abstract

Duchenne muscular dystrophy (DMD) is the most prevalent neuromuscular disease diagnosed in childhood. It is a progressive and wasting disease, characterized by a degeneration of skeletal and cardiac muscles caused by the lack of dystrophin protein. The absence of this crucial structural protein leads to sarcolemmal fragility, resulting in muscle fiber damage during contraction. Despite ongoing efforts, there is no cure available for DMD patients. One of the primary challenges is the limited efficacy of current preclinical tools, which fail in modeling the biological complexity of the disease. Human-based three-dimensional (3D) cell culture methods appear as a novel approach to accelerate preclinical research by enhancing the reproduction of pathophysiological processes in skeletal muscle. In this work, we developed a patient-derived functional 3D skeletal muscle model of DMD that reproduces the sarcolemmal damage found in the native DMD muscle. These bioengineered skeletal muscle tissues exhibit contractile functionality, as they responded to electrical pulse stimulation. Sustained contractile regimes induced the loss of myotube integrity, mirroring the pathological myotube breakdown inherent in DMD due to sarcolemmal instability. Moreover, damaged DMD tissues showed disease functional phenotypes, such as tetanic fatigue. We also evaluated the therapeutic effect of utrophin upregulator drug candidates on the functionality of the skeletal muscle tissues, thus providing deeper insight into the real impact of these treatments. Overall, our findings underscore the potential of bioengineered 3D skeletal muscle technology to advance DMD research and facilitate the development of novel therapies for DMD and related neuromuscular disorders.

Subject

Distròfia muscular, Enginyeria de teixits, Cultiu cel·lular

Subject (English)

Muscular dystrophy, Tissue engineering, Cell culture

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Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

Citation

TEJEDERA VILLAFRANCA, Ainoa, et al. Mimicking sarcolemmal damage in vitro: a contractile 3D model of skeletal muscle for drug testing in Duchenne muscular dystrophy. BIOFABRICATION. 2023. Vol. 15, num. 4, pags. 45024. ISSN 1758-5090. [consulted: 8 of August of 2026]. Available at: https://hdl.handle.net/2445/202898

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