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Reactivated Fetal Gene Triggers Division of Adult Human Heart Cells in Lab

The Mount Sinai team will pursue safety testing ahead of an FDA application for early human trials.

Overview

  • Peer-reviewed data in npj Regenerative Medicine show that delivering Cyclin A2 (CCNA2) via a human-compatible, replication-deficient viral vector induced orderly cell division in adult human cardiomyocytes from 41- and 55-year-old donor hearts.
  • Time-lapse imaging and calcium assays confirmed daughter cells retained sarcomere structure and normal electrical activity, indicating functional integrity after division.
  • Single-nucleus and transcriptomic analyses suggest CCNA2 briefly reactivates fetal-like cell-cycle programs to enable cytokinesis, with signals consistent with a self-limiting proliferative window.
  • Cells from a 21-year-old donor did not divide with CCNA2, aligning with evidence that younger adult hearts have baseline regenerative capacity without this stimulus.
  • The work builds on a 2014 pig study showing post-infarct regeneration with CCNA2, and researchers now plan formal preclinical safety and toxicology studies, with key challenges including targeted delivery, dose control, and long-term arrhythmic and oncogenic risk assessment.