PXD061757

PXD061757 is an original dataset announced via ProteomeXchange.

Title	Biofabrication of a 3D Human Skeletal Muscle Microenvironment to Study the Early Steps of Fibrosis
Description	Skeletal muscle fibrosis is a prevalent characteristic of aging and dystrophies. Beyond myofibroblast involvement, recent findings highlighted a complex cellular cross-talk within the muscle microenvironment, finally resulting in vascular and tissue damage. This complexity is not captured by current in vitro models which are focused on myobundle biofabrication, hence compromising the development of new therapies. We biofabricated human fibrotic muscle microenvironments integrated within a microphysiological system embedding a novel pillar setup coupled with a custom-made electrical stimulation for triggering contraction in up to 36 samples. Combination of imaging-based and RNAseq analyses demonstrated high myobundle maturation with upregulated genes connected with sarcomere organization/muscle contractility. Dystrophic fibroblasts impaired muscle contraction, a phenomenon partially reversed with Nintedanib. Indeed, biochemical assays and mass-spec demonstrated reduced collagen deposition and improved mitochondrial functionality upon treatment, resulting in restored contractility. Analysis of the stromal compartment, which includes microvascular networks with dystrophic fibroblasts or M1-polarized macrophages, revealed activation of endothelial-mesenchymal transition. Indeed, retrieved endothelial cells analyzed through flow cytometry, qPCR and immunofluorescence showed upregulation of mesenchymal markers associated with vascular damage. The biofabricated model combined contractile myobundles with a complex stromal compartment and demonstrated its potential for repurposing an anti-fibrotic drug and analyzing mechanisms of muscle microenvironment damage.
HostingRepository	PRIDE
AnnounceDate	2025-10-31
AnnouncementXML	Submission_2025-10-31_04:35:34.094.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matteo Pecoraro
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-12 05:25:45	ID requested
⏵ 1	2025-10-31 04:35:35	announced

Francescato R, Ishmaku M, Tal, ò G, Francese M, Cascione L, Martini V, Uguccioni M, Moretti M, Bersini S, Biofabrication of a 3D human skeletal muscle microenvironment to study the early steps of fibrosis. Mater Today Bio, 35():102386(2025) [pubmed]

10.1016/j.mtbio.2025.102386;

submitter keyword: Biofabrication, Endothelial-mesenchymal transition, Microphysiological system, Skeletal muscle, Microvascular network

Simone Bersini
contact affiliation	Regenerative Medicine Technologies Lab, Laboratories for Translational Research (LRT), Ente Ospedaliero Cantonale, Bellinzona (CH); Servizio di Ortopedia e Traumatologia, Ente Ospedaliero Cantonale, Lugano (CH); Euler Institute, Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano (CH)
contact email	simone.bersini@eoc.ch
lab head
Matteo Pecoraro
contact affiliation	Institute for Research in Biomedicine, Via Francesco Chiesa 5 - CH-6500 Bellinzona
contact email	matteo.pecoraro@irb.usi.ch
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD061757

PRIDE project URI

• PRIDE
  1. PXD061757
     1. Label: PRIDE project
     2. Name: Biofabrication of a 3D Human Skeletal Muscle Microenvironment to Study the Early Steps of Fibrosis