OSK-mediated partial reprogramming induces cardiomyocyte dedifferentiation, overcomes cytokinesis barriers, and promotes post-MI endogenous cardiac regeneration.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and animal experimental research
PubMed 42013916 · doi:10.1016/j.yjmcc.2026.04.005
What was done
The authors evaluated the effects of transient partial reprogramming using three Yamanaka factors (OSK: OCT4, SOX2, KLF4, omitting c-Myc) in cardiomyocytes (CMs) both in vitro and in vivo in an experimental myocardial infarction (MI) model. They assessed cell-cycle entry, dedifferentiation, sarcomere structure, cytokinesis completion, and post-MI cardiac repair.
What was found
The abstract reports no numerical values. OSK overexpression did not directly trigger CM S-phase entry or cell-cycle re-entry. Instead, it induced cardiomyocyte dedifferentiation marked by sarcomere disassembly. This priming overcame cytokinesis barriers in proliferating CMs in vitro and in vivo, generating mononuclear CMs with high proliferative potential and enhancing post-MI cardiac repair.
Why it matters
Excluding the proto-oncogene c-Myc removes a major tumorigenic safety barrier associated with standard Yamanaka-factor reprogramming. Showing that OSK acts specifically by priming dedifferentiation and resolving cytokinesis bottlenecks provides a safer framework for endogenous cardiac regeneration research.
Limits
The abstract provides no sample sizes, animal species details, or quantitative measurements of cardiac functional recovery. As an early-stage preclinical study in cells and animal models, safety, vector delivery feasibility, and efficacy in humans remain unestablished.
Cited by
- supports Partial cellular reprogramming using three Yamanaka factors has been successfully replicated in the cardiac system of mice.