In vivo-like scaffold-free 3D in vitro Models of Muscular Dystrophies: The Case for Anchored Cell Sheet Engineering in Personalized Medicine

ABSTRACT: The study of muscle dystrophies, including Duchenne and Myotonic dystrophies, has faced significant challenges due to the lack of physiologically relevant in vitro models. This research introduces a novel, scaffold- and biomaterial-free platform based on cell sheet engineering to create in vitro models using patient-specific cells. This innovative approach, known as anchored cell sheet engineering, offers a comprehensive biofabrication method that replicates mature cell phenotypes and tissue-specific extracellular matrix (ECM) deposited by the cells themselves. Primary cells from both healthy individuals and patients with Duchenne and Myotonic dystrophy type 1 were used to develop robust anchored 3D muscle fibers. The models were extensively characterized using proteomics analysis revealing that they form mature constructs closely resembling in vivo conditions, surpassing traditional 2D cultures in translational potential. Disease-specific models effectively captured key phenotypic features of the respective dystrophies. Additionally, therapeutic treatments led to significant proteomic profile changes, documented using custom Python scripts. This scaffold-free 3D modeling technique offers a promising platform for advancing muscle dystrophy research and improving drug screening methodologies for developing new treatments for complex diseases with better translatability for clinical applications.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skeletal Muscle, Skeletal Muscle Myoblast In Skeletal Muscle

DISEASE(S): Myotonic Dystrophy Type 1,Duchenne Muscular Dystrophy

SUBMITTER: Alireza Shahin-Shamsabadi  

LAB HEAD: Alireza Shahin-Shamsbaadi

PROVIDER: PXD052728 | Pride | 2024-12-24

REPOSITORIES: Pride