Latest developments in engineered skeletal muscle tissues for drug discovery and development

ABSTRACT

Introduction

With the advances in skeletal muscle tissue engineering, new platforms have arisen with important applications in biology studies, disease modeling, and drug testing. Current developments highlight the quest for engineering skeletal muscle tissues with higher complexity . These new human skeletal muscle tissue models will be powerful tools for drug discovery and development and disease modeling.

Areas covered

The authors review the latest advances in in vitro models of engineered skeletal muscle tissues used for testing drugs with a focus on the use of four main cell culture techniques: Cell cultures in well plates, in microfluidics, in organoids, and in bioprinted constructs. Additional information is provided on the satellite cell niche.

Expert opinion

In recent years, more sophisticated in vitro models of skeletal muscle tissues have been fabricated. Important developments have been made in stem cell research and in the engineering of human skeletal muscle tissue. Some platforms have already started to be used for drug testing, notably those based on the parameters of hypertrophy/atrophy and the contractibility of myotubes. More developments are expected through the use of multicellular types and multi-materials as matrices . The validation and use of these models in drug testing should now increase.

KEYWORDS:

• Bioprinting
• drug development
• drug evaluation
• microfluidics
• muscle skeletal
• organoids
• stem cells

Article highlights

• The development of protocols to culture and differentiate stem cells has allowed for, in vitro, human skeletal muscle tissues to be engineered.

• Among the main techniques used to engineer skeletal muscle tissues are cell cultures in well-plate between anchors, in microfluidics, in organoids, and in bioprinted constructs.

• Each of these techniques offers a different level of skeletal muscle tissue complexity with specific advantages that can be useful for drug discovery.

• The satellite cell niche changes during muscle regeneration and many factors and cells interact with these satellite cells

• Significant developments in the use of patient cells for personalized medicine and human disease modeling have been made.

• Several drugs inducing the hypertrophy/atrophy of myotubes or affecting their contractibility have already been tested on these skeletal tissue models.

• More sophisticated skeletal muscle tissues models are now in development while the validation and the testing of drugs using this type of model should increase.

This box summarizes key points contained in the article.

Declaration of Interest

The authors declare technical assistance from the Drug Formulation Unit (U10) at the University of the Basque Country (UPV/EHU). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Numbers 22K18936 and 21K04852); AMED (Grant Number JP21gm1310001); JST Adaptable and Seamless Technology Transfer Program through Target-driven R&D (Grant Numbers JPMJTM22BD and JPMJTM22BE); CASIO SCIENCE PROMOTION FOUNDATION, and the Research Center for Biomedical Engineering at Tokyo Medical and Dental University, Japan. Furthermore, G Orive thanks the Spanish Ministry of Economy, Industry, and Competitiveness (PID2019-106094RB-I00/AEI/10.13039/501100011033) for their support.