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Bioengineering an Innervated 3D Skeletal Muscle Model to Replicate Contractile Dysfunction in Neuromuscular Disorders

Project description

Muscle research to fight neuromuscular disease

Neuromuscular disorders (NMDs) impair movement and shorten lives. The discovery of a treatment is slowed due to a lack of reliable lab models that mimic the complex interplay between muscles and nerves. Backed by the Marie Skłodowska-Curie Actions programme, the InnervateNMD project will develop humanised, innervated muscle models using 3D tissue engineering. Combining lab-grown muscle and motor neurons derived from stem cells, the project will recreate functioning neuromuscular junctions, which are critical for muscle contraction. These bioengineered models, enhanced with 3D-printing and advanced electrode arrays, will be tested on Charcot-Marie-Tooth disease. If successful, they could transform how scientists study NMDs and pave the way for new therapies.

Objective

Neuromuscular disorders (NMDs) encompass a diverse group of diseases that severely impact patients' quality of life and reduce life expectancy. Despite the urgent need, only a handful of these disorders are currently treatable. A major barrier to therapeutic development is the lack of humanized models that can accurately reflect the complex neuromuscular phenotypes observed in patients.
Recent advancements in cell culture techniques have enabled the development of functional 3D-tissue-engineered skeletal muscles (3D-TESMs), offering a promising platform to study NMDs. However, the integration of motor neurons and neuromuscular junctions (NMJs) in these models remains challenging. In this project, I aim to bridge this critical gap by leveraging my background in developing in vitro muscle models and the host lab's expertise in peripheral nerve biology. Together, we will develop innervated cell models capable of contractile functioning using human-induced pluripotent stem cell-derived muscle cells and motor neurons. By integrating 3D-printing technologies and a customized high-density multielectrode array, I plan to generate two innervated 3D-TESM cell models to study both the muscular and neuronal aspects of NMDs.
As a proof-of-concept, these models will be applied to study the effects of axonal Charcot-Marie-Tooth disease (CMT2), illustrating their potential for investigating NMDs. Overall, the development of innervated 3D-TESMs will represent a significant step forward in creating more accurate humanized systems to study NMDs and accelerate the development of effective therapeutics.

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERSITEIT ANTWERPEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 200 400,00
Address
PRINSSTRAAT 13
2000 Antwerpen
Belgium

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Region
Vlaams Gewest Prov. Antwerpen Arr. Antwerpen
Activity type
Higher or Secondary Education Establishments
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Total cost

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