Adv Exp Med Biol. 2026 ;1509 179-216
Cell fusion has evolved at an exciting pace over the past 50 years. From experimental studies in vitro, later applications in vivo, and various discoveries of innate in vivo cell fusion, this field continues to expand, particularly as biotechnological strategies advance. Initially developed as an experimental approach to study nuclear reprogramming, cell fusion provided some of the first and most convincing evidence that differentiated somatic nuclei are still reprogrammable. Fusion-based systems changed long-held beliefs about the stability of cell fate by demonstrating that significant transcriptional, epigenetic, and chromatin changes can occur within hours. Subsequent in vivo studies demonstrated that similar fusion events occur naturally in adult tissues, principally in response to injury, inflammation, or degenerative stress. In the context of regeneration, cell fusion has emerged as an important and previously under-recognized mechanism underlying cellular plasticity, tissue repair, and functional recovery.In this chapter, we discuss the molecular and cellular mechanisms that control cell fusion, the experimental tools used to study it, and the insights gained from fusion-based models of reprogramming. We further examine the growing evidence supporting the role of cell fusion in tissue regeneration across multiple organs, including the liver, muscle, nervous system, and heart. Finally, we address the challenges, limitations, and safety considerations that currently restrict therapeutic translation and outline future directions for understanding and applying cell fusion in regenerative biology.
Keywords: Cell fusion; Polyploidy; Regeneration; Reprogramming