Food research international (Ottawa, Ont.)Oct 23, 2026

Better long-term growth and muscle development of cow muscle stem cells by editing the CDKN2A gene

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 24, 2026

Abstract

Prolonged in vitro culture results in cellular senescence in bovine muscle stem cells, impairing their growth and muscle-forming ability.

Cellular senescence in bovine muscle stem cells is associated with reduced proliferation and myogenic potential.
Upregulation of the cyclin-dependent kinase inhibitor CDKN2A occurs during cell passaging.
Knockout of CDKN2A substantially enhances the expansion of bovine muscle stem cells.
CDKN2A-knockout cell lines demonstrate significantly improved long-term proliferation and lower expression of cyclin-dependent kinase inhibitors compared to wild-type cells.
These knockout cells show increased expression of muscle-specific regulatory factors and better muscle cell differentiation in both low-serum and serum-free conditions.
In a serum-free three-dimensional hydrogel, CDKN2A-knockout cells form more muscle fibers compared to wild-type cells without exhibiting tumor-like growth.

Simplified

The production of cultured meat is constrained by the limited proliferation and differentiation capacity of seed cells. Here, we report that prolonged in vitro culture induces cellular senescence in bovine muscle stem cells (bMuSCs), impairing their proliferative and myogenic potential. We then examined the expression of cyclin-dependent kinase inhibitors (CKIs) and found that CDKN2A expression was markedly upregulated during passaging and its knockout substantially enhanced the expansion of bMuSCs. Subsequently, we established two CDKN2A-knockout (CDKN2A-KO) monoclonal cell lines, which showed significantly enhanced proliferation over long-term culture and exhibited an overall reduction in the expression of CKIs compared to wild-type (WT) controls. Further, CDKN2A-KO bMuSCs displayed elevated expression of myogenic regulatory factors and improved myogenic differentiation under both low-serum and serum-free conditions. Notably, in a serum-free three-dimensional hydrogel system, CDKN2A-KO cells showed enhanced myotube formation in comparison with WT cells. Moreover, CDKN2A knockout did not induce anchorage-independent growth, indicating a non-tumorigenic phenotype in these cells. These results demonstrate that targeting CDKN2A effectively delays cellular senescence and enhances the myogenic potential of bMuSCs without tumorigenic risk, providing a promising strategy to improve large-scale cell expansion for cultured meat.

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Better long-term growth and muscle development of cow muscle stem cells by editing the CDKN2A gene

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