Cancer cell-dependent increase in senescence-like populations following exosome treatment from bone marrow and induced pluripotent stem cell-derived mesenchymal stem cells

doi:10.4252/wjsc.v17.i11.110381

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Nov 26, 2025 (publication date) through Nov 26, 2025

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World Journal of Stem Cells

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1948-0210

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Stem Cells. Nov 26, 2025; 17(11): 110381
Published online Nov 26, 2025. doi: 10.4252/wjsc.v17.i11.110381

Cancer cell-dependent increase in senescence-like populations following exosome treatment from bone marrow and induced pluripotent stem cell-derived mesenchymal stem cells

Nidaa A Ababneh, Sura Nashwan, Razan AlDiqs, Mohammad A Ismail, Ahmed A Abdulelah, Anas H A Abu-Humaidan, Lina AlQirem, Khairallah Al-Abdallat, Talal Al-Qaisi, Tareq Saleh, Abdalla Awidi

Nidaa A Ababneh, Sura Nashwan, Mohammad A Ismail, Abdalla Awidi, Cell Therapy Center, University of Jordan, Amman 11942, Jordan

Razan AlDiqs, Department of Allied Sciences, Faculty of Arts and Sciences, Al-Ahliyya Amman University, Amman 19111, Jordan

Mohammad A Ismail, South Australian ImmunoGENomics Cancer Institute, Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia

Ahmed A Abdulelah, Lina AlQirem, School of Medicine, University of Jordan, Amman 11942, Jordan

Ahmed A Abdulelah, Royal Papworth Hospital NHS Foundation Trust, Royal Papworth Hospital, Cambridge CB2 0AY, United Kingdom

Anas H A Abu-Humaidan, Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, University of Jordan, Amman 11942, Jordan

Lina AlQirem, University of Arkansas for Medical Sciences, Arkansas City, KS 72205, United States

Khairallah Al-Abdallat, Bone Marrow Transplantation Unit, Jordan University Hospital, Amman 11942, Jordan

Khairallah Al-Abdallat, Abdalla Awidi, Hemostasis and Thrombosis Laboratory, School of Medicine, University of Jordan, Amman 11942, Jordan

Talal Al-Qaisi, Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi 59911, United Arab Emirates

Tareq Saleh, Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences Manama, Arabian Gulf University, Manama 329, Bahrain

Tareq Saleh, Department of Pharmacology and Public Health, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan

Abdalla Awidi, Department of Hematology and Oncology, Jordan University Hospital, Amman 11942, Jordan

Author contributions: Ababneh NA and Awidi A conceptualized the study and supervised the study; Ababneh NA, Nashwan S, and Ismail MA carried out the experiments; Nashwan S and AlDiqs R wrote the initial draft of the manuscript; Ababneh NA, AlDiqs R, Abdulelah AA, Abu-Humaidan AHA, AlQirem L, Al-Abdallat K, Al-Qaisi T, and Saleh T revised and edited the manuscript; Ababneh NA, AlDiqs R, and Saleh T performed the formal analysis and results interpretation; All authors read and approved the final version of the publication.

Institutional review board statement: This study fully adhered to ethical standards and guidelines. It received approval from the Institutional Review Board, No. IRB-CTC/2-2021/06 at the Cell Therapy Center, University of Jordan in accordance with the Declaration of Helsinki.

Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.

Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Nidaa A Ababneh, Associate Professor, Cell Therapy Center, University of Jordan, Queen Rania Street, Amman 11942, Jordan. n.ababneh@ju.edu.jo

Received: June 7, 2025
Revised: July 29, 2025
Accepted: October 9, 2025
Published online: November 26, 2025
Processing time: 173 Days and 5.1 Hours

Abstract

BACKGROUND

Mesenchymal stem cell (MSC) extracellular vesicles, particularly exosomes (Exos), are gaining recognition as promising therapeutic tools for cancer due to their capacity to modulate tumor cell biology. Induced pluripotent stem cell-derived MSCs (iMSCs) revealed therapeutic characteristics compared with conventional MSCs due to their proliferative capacity and enhanced differentiation potential.

AIM

To study the impact of Exos derived from iMSCs (iMSC-Exos) and bone marrow MSCs (BMSC-Exos) on PANC1 and MDA-MB-231 cancer cells.

METHODS

The iMSCs and BMSCs were characterized based on the International Society for Cellular Therapy (2006) criteria by verifying the expression of MSC-specific markers and their differentiation potential. Exos were isolated from 48-hour conditioned media using sequential ultracentrifugation and characterized based on size, morphology, and expression of surface markers including CD9, CD81, and CD63. PANC1 and MDA-MB-231 cells were treated with the isolated Exos, and their effects on cell proliferation, apoptosis, senescence, and invasion were assessed.

RESULTS

In PANC1 cells iMSC-Exos sustained antiproliferative activity for 48 hours (35% reduction, P < 0.01) while BMSC-Exos had a transient effect. In MDA-MB-231 cells, both Exos lowered proliferation significantly after 48 hours (~28% and ~22% reduction, P < 0.05). Notably, these antiproliferative effects were not associated with apoptosis, but an increase in senescence-like tumor cells was identified as the primary response with iMSC-Exos inducing approximately 2.3-fold higher number of senescence-associated β-galactosidase-positive cells compared with BMSC-Exos across both cancer cell lines. Tumor cell invasion was markedly inhibited in PANC1 and MDA-MB-231 cells in response to iMSC-Exos (~60% and ~45% reduction, respectively, P < 0.001), and only in PANC1 cells in response to BMSC-Exos.

CONCLUSION

iMSC-Exos effectively inhibited tumor proliferation and invasion via a senescence-like mechanism. These results indicated that iMSC-Exos could serve as a cell-free cancer therapy and merit further animal model evaluation.

Keywords: Bone marrow-derived stromal cells; Induced pluripotent stem cell-derived mesenchymal stem cells; Cell-free cancer therapy; Exosomes; Breast cancer; Pancreatic cancer; Senescence-associated secretory phenotype

Core Tip: This study explored the effects of exosomes (Exos) obtained from bone marrow mesenchymal stem cells (MSCs) and MSCs derived from induced pluripotent stem cells on pancreatic and triple-negative breast cancer cells. Exos obtained from MSCs derived from induced pluripotent stem cells exhibited a stronger and sustained antiproliferative effect by inducing a senescence-like state without apoptosis. In contrast, bone marrow MSC-derived Exos showed variable effects depending on cancer type. These findings highlight the importance of Exos source in determining therapeutic outcomes and suggest senescence induction as a key response to Exos exposure.