Dataset Information

Biofabrication of a 3D Human Skeletal Muscle Microenvironment to Study the Early Steps of Fibrosis

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skeletal Muscle

SUBMITTER: Matteo Pecoraro

LAB HEAD: Simone Bersini

PROVIDER: PXD061757 | Pride | 2025-10-31

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20241212_MP197_MeIs_SA_DIA_H12_DMD_3333.d.zip	Other
	20241212_MP197_MeIs_SA_DIA_H12_DMD_N_3339.d.zip	Other
	20241212_MP197_MeIs_SA_DIA_H12_FH_3327.d.zip	Other
	20241212_MP197_MeIs_SA_DIA_H12_HSMM_3321.d.zip	Other
	20241212_MP197_MeIs_SA_DIA_H7_DMD_3329.d.zip	Other

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Biofabrication of a 3D human skeletal muscle microenvironment to study the early steps of fibrosis.

Francescato R R Ishmaku M M Talò G G Francese M M Cascione L L Martini V V Uguccioni M M Moretti M M Bersini S S

Materials today. Bio 20251015

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PMID: 41158711

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