Kim JS, Hwang IS, Kim SJ, Moon MH, Park HD, Jin BH, Kim DY, Lee MJ, Eum SY, Yoo SJ, Cha BH. Cell-cell fusion and stem cell plasticity: Emerging paradigms in tissue regeneration. World J Stem Cells 2026; 18(5): 118307 [DOI: 10.4252/wjsc.v18.i5.118307]
Corresponding Author of This Article
Byung-Hyun Cha, PhD, Assistant Professor, Department of Biomedical Systems Science, College of Biomedical Science, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, 24341, South Korea. bhcha@kangwon.ac.kr
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Cell & Tissue Engineering
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review-article
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Kim JS, Hwang IS, Kim SJ, Moon MH, Park HD, Jin BH, Kim DY, Lee MJ, Eum SY, Yoo SJ, Cha BH. Cell-cell fusion and stem cell plasticity: Emerging paradigms in tissue regeneration. World J Stem Cells 2026; 18(5): 118307 [DOI: 10.4252/wjsc.v18.i5.118307]
World J Stem Cells. May 26, 2026; 18(5): 118307 Published online May 26, 2026. doi: 10.4252/wjsc.v18.i5.118307
Cell-cell fusion and stem cell plasticity: Emerging paradigms in tissue regeneration
Ji Seob Kim, In Sun Hwang, Seo Jeong Kim, Min Hee Moon, Hae-Dam Park, Byeong Ho Jin, Da Young Kim, Min Ji Lee, Se-Yun Eum, Seo-Jin Yoo, Byung-Hyun Cha
Ji Seob Kim, In Sun Hwang, Seo Jeong Kim, Min Hee Moon, Hae-Dam Park, Byeong Ho Jin, Da Young Kim, Min Ji Lee, Se-Yun Eum, Seo-Jin Yoo, Byung-Hyun Cha, Department of Biomedical Systems Science, College of Biomedical Science, Kangwon National University, Chuncheon-si, 24341, South Korea
Co-first authors: Ji Seob Kim and In Sun Hwang.
Author contributions: Kim JS and Hwang IS contributed equally to the development and writing of this review and are therefore recognized as co-first authors; Kim SJ, Moon MH, Park HD, Jin BH, Kim DY, Lee MJ, Eum S, and Yoo S prepared the figures and graphical illustrations; Cha BH supervised the entire project, critically reviewed and finalized the manuscript, and secured research funding.
Supported by the National Research Foundation of Korea Grant funded by the Korea Government (MSIT), No. RS-2023-00277856; and the grant of the Korea Health Technology R&D Project Through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea, No. RS-2025-24535069.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Byung-Hyun Cha, PhD, Assistant Professor, Department of Biomedical Systems Science, College of Biomedical Science, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, 24341, South Korea. bhcha@kangwon.ac.kr
Received: December 29, 2025 Revised: January 20, 2026 Accepted: March 2, 2026 Published online: May 26, 2026 Processing time: 147 Days and 18.4 Hours
Abstract
Cell-cell fusion is a fundamental biological process contributing to tissue development, homeostasis, and regeneration. Physiological fusion in the placenta, skeletal muscle, bone, and immune system is mediated by tightly regulated fusogens and microenvironmental cues. Dysregulated fusion, however, can lead to pathological outcomes, including malignant cell hybrids and viral syncytia. Stem cell-somatic cell fusion represents both a therapeutic opportunity and a safety concern, as fusion-derived heterokaryons and synkaryons can enhance tissue repair and plasticity while posing risks of genomic instability and unintended fusion events. In this review, we synthesize current knowledge on the molecular mechanisms, tissue-specific fusogens, and regulatory programs governing cell fusion. We also discuss translational strategies for harnessing stem cell fusion in regenerative therapies, highlighting opportunities to maximize repair while minimizing potential risks. Our goal is to provide a unified framework that integrates physiological and pathological perspectives, offering guidance for future research and clinical application.
Core Tip: This review summarizes the status quo of cell-cell fusion across development, regeneration, and disease. We highlight key topics including membrane merger mechanisms, tissue-specific fusogens, and microenvironmental cues that influence fusion competence and post-fusion behavior. Stem cell-somatic cell fusion presents a dual-edged opportunity: Fusion-derived heterokaryons (multinuclear cells) and synkaryons (nuclear-mixed hybrids) may enhance repair and plasticity, yet raise safety concerns including genomic instability and unintended fusion events. Major progress has clarified core fusion stages and identified physiological fusogens, but critical problems remain in vivo gating, fate/stability prediction, and pathological risks (malignant hybrids, viral syncytia).
