Mechanoepigenetic Targeting of Histone Methyltransferase EZH2 Increases Potential of Scalable Manufacturing in Human Derived Primary Mesenchymal Stromal Cells.

ABSTRACT: Manufacturing clinical grade mesenchymal stromal cells (MSCs) remains a major bottleneck for cell-based therapies, as extensive in-vitro expansion on standard tissue-culture plastic (TCP) drives loss of stemness, reduced immunomodulatory activity, and diminished therapeutic efficacy. Although substrate stiffness is known to influence MSC fate through mechanotransduction, the epigenetic mechanisms linking mechanical stress to progressive phenotypic drift remain poorly defined. A mechano-epigenetic pathway is identified in this work, centered on the histone methyltransferase EZH2 - that governs chromatin remodeling and loss of stemness during serial passaging. Multi-omics, high-resolution imaging, and functional assays show that MSCs expanded on mechanically stiff TCP accumulate H3K27me3 rep

SUBMITTER: Monroe L 

PROVIDER: S-EPMC12709483 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature