Wang SF, Guo HC, Gong XQ, Peng XW. Induced pluripotent stem cell-derived mesenchymal stem cell exosomes emerge as potent inducers of cancer cell senescence. World J Stem Cells 2026; 18(9): 115628 [DOI: 10.4252/wjsc.115628]
Corresponding Author of This Article
Xiang-Wen Peng, PhD, Associate Professor, Central Laboratory, Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, No. 416 Chengnan East Road, Yuhua District, Changsha 410001, Hunan Province, China. pxw1237@163.com
Research Domain of This Article
Biology
Article-Type of This Article
editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Si-Feng Wang, Xiang-Wen Peng, Central Laboratory, Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha 410001, Hunan Province, China
Hai-Chun Guo, Xiao-Qin Gong, Changsha Maternal and Child Health Care Hospital, Hunan Normal University, Changsha 410001, Hunan Province, China
Co-first authors: Si-Feng Wang and Hai-Chun Guo.
Co-corresponding authors: Xiao-Qin Gong and Xiang-Wen Peng.
Author contributions: Peng XW conceived the idea and wrote the original draft of the editorial; Wang SF, Guo HC, Gong XQ, and Peng XW critically reviewed, revised, and finalized the manuscript for intellectual content and accuracy. Wang SF and Guo HC contributed equally to this manuscript and are co-first authors. Gong XQ and Peng XW contributed equally to this manuscript and are co-corresponding authors. All authors approved the final version and agree to be accountable for all aspects of the work.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Xiang-Wen Peng, PhD, Associate Professor, Central Laboratory, Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, No. 416 Chengnan East Road, Yuhua District, Changsha 410001, Hunan Province, China. pxw1237@163.com
Received: October 21, 2025 Revised: November 25, 2025 Accepted: January 26, 2026 Published online: September 26, 2026 Processing time: 338 Days and 6.1 Hours
Abstract
This editorial provides a critical commentary on the study published by Ababneh et al. Mesenchymal stem cells (MSCs) are among the most prolific producers of exosomes (Exos), nanoscale extracellular vesicles that combine tumor-homing capacity with minimal immunogenicity, no tumorigenic risk, and favorable ethical and logistical profiles compared to whole-cell therapies. Ababneh et al demonstrate that Exos derived from induced pluripotent stem cell-derived MSCs (iMSC-Exos) exert a robust and sustained anti-proliferative effect on both pancreatic (PANC1) and triple-negative breast cancer (MDA-MB-231) cells not by triggering apoptosis, but by inducing a stable senescence-like state. Strikingly, bone marrow MSC-derived Exos show inconsistent, cancer type-dependent responses, underscoring a pivotal principle that the cellular origin of Exos is not a technical detail but a decisive determinant of their biological function. This work challenges the long-standing assumption that MSC-derived Exos are therapeutically interchangeable and repositions “therapy-induced senescence”, a durable cell cycle arrest coupled with a complex secretory program, as a novel, cell-free anticancer strategy. Critical questions remain: What molecular cargoes (e.g., non-coding RNAs, senescence-associated secretory phenotype regulators) in iMSC-Exos drive this phenotype? Can this non-lytic approach avoid the inflammatory toxicity of pro-apoptotic therapies? Most crucially, will therapy-induced senescent cells be efficiently cleared by immune surveillance, or could their senescence-associated secretory phenotype inadvertently fuel tumor progression? Despite these unknowns, iMSC-Exos represent more than a new biologic: They embody a conceptual leap, positioning “therapeutic senescence” as a source-dependent, tunable modality with the potential to catalyze a new era of precision Exos-based oncology.
Core Tip: This editorial emphasizes how exosomes from induced pluripotent stem cell-derived mesenchymal stem cells, not those from bone marrow, drive a potent, non-apoptotic antitumor response by inducing stable senescence in aggressive carcinomas, thereby redefining exosome source as a critical therapeutic variable and positioning senescence induction as a promising strategy for precision cancer therapy.
