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Review Article | Open Access

Unraveling the role of PIWI/piRNAs in stem cell therapy: Epigenetic mechanisms and therapeutic potentials

Ying Yanga,d, Xiangping Luoa,d, Ermao Lia, Zhengmao Lib, Feiyan Zoua, Jiayang Liaoa, Yizhi Wua, Bo Weia( )
Institute of Translational Medicine, School of Basic Medicine, Department of Special Medicine, School of Public Health, Hengyang Medical College, University of South China, Heneyang Central Hospital, Hengyang, Hunan 42100l, China
Department of Orthopaedics Trauma, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China

d These authors contributed equally to this work.

Peer review under the responsibility of Chongqing Medical University.

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Abstract

The therapeutic potential of stem cell therapy critically depends on precise epigenetic regulation mediated by PIWI/piRNA complexes. This review synthesizes current literature to analyze the structure, interaction mechanisms, and epigenetic functions of PIWI proteins and their associated piRNAs (24–32 nt non-coding RNAs), with emphasis on stem cell therapy and disease modeling applications. PIWI/piRNA complexes critically regulate transcriptional control, chromatin remodeling, and stem cell plasticity. These complexes maintain stemness while promoting differentiation, serving as key biomarkers and therapeutic targets in cancers and skeletal disorders. However, translational challenges regarding specificity, delivery stability, and safety profiles persist. Advancing PIWI/piRNA-based therapeutics requires innovative technologies and expanded clinical validation to develop safe, targeted stem cell treatments for diverse pathologies.

Keywords

Epigenetic regulationpiRNAPIWI proteinsPIWI/piRNA complexesStem cell therapy

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Genes & Diseases
Volume 13 Issue 5,
September 2026
DOI: 10.1016/j.gendis.2025.101854

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Cite this article:
Yang Y, Luo X, Li E, et al. Unraveling the role of PIWI/piRNAs in stem cell therapy: Epigenetic mechanisms and therapeutic potentials. Genes & Diseases, 2026, 13(5). https://doi.org/10.1016/j.gendis.2025.101854

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Received: 13 April 2025
Revised: 24 July 2025
Accepted: 12 August 2025
Published: 18 September 2025
© 2025 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).