Mesenchymal Stem Cell-derived Exosomes in Cancer Therapy Resistance: Recent Advances and Therapeutic Potential

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2022 Sep 13

PMID 36100944

Authors

Zhengjun Lin

Yanlin Wu

Yiting Xu

Guoqing Li

Zhihong Li

Tang Liu

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be obtained from various human tissues and organs. They can differentiate into a wide range of cell types, including osteoblasts, adipocytes and chondrocytes, thus exhibiting great potential in regenerative medicine. Numerous studies have indicated that MSCs play critical roles in cancer biology. The crosstalk between tumour cells and MSCs has been found to regulate many tumour behaviours, such as proliferation, metastasis and epithelial-mesenchymal transition (EMT). Multiple lines of evidence have demonstrated that MSCs can secrete exosomes that can modulate the tumour microenvironment and play important roles in tumour development. Notably, very recent works have shown that mesenchymal stem cell-derived exosomes (MSC-derived exosomes) are critically involved in cancer resistance to chemotherapy agents, targeted-therapy drugs, radiotherapy and immunotherapy. In this review, we systematically summarized the emerging roles and detailed molecular mechanisms of MSC-derived exosomes in mediating cancer therapy resistance, thus providing novel insights into the clinical applications of MSC-derived exosomes in cancer management.

Citing Articles

Mesenchymal Stem Cell-Derived Exosomes in Cancer Resistance Against Therapeutics.

Easwaran V, Pai K, Pai K Cancers (Basel). 2025; 17(5).

PMID: 40075675 PMC: 11898417. DOI: 10.3390/cancers17050831.

Engineered exosomes restore miR-508-5p expression in uterine corpus endometrial carcinoma and reduce tumor progression and metastasis by targeting DLL3.

Li Y, Liu H, Feng J, Tian W, Du J, Zhang L Front Oncol. 2025; 15:1532564.

PMID: 40066092 PMC: 11891050. DOI: 10.3389/fonc.2025.1532564.

Exosomal miR-125b-5p derived from mesenchymal stromal/stem cell enhances anti-PD-1 therapy in mouse colon cancer model.

Jiang M, Liu J, Hu S, Yan X, Cao Y, Wu Z Stem Cell Res Ther. 2025; 16(1):112.

PMID: 40038776 PMC: 11881248. DOI: 10.1186/s13287-025-04227-3.

Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells.

Balaraman A, Babu M, Afzal M, Sanghvi G, M M R, Gupta S Regen Ther. 2025; 28:558-572.

PMID: 40034540 PMC: 11872554. DOI: 10.1016/j.reth.2025.01.019.

Immunomodulatory effects of mesenchymal stem cell therapy in chronic kidney disease: a literature review.

Li J, Wu M, He L BMC Nephrol. 2025; 26(1):107.

PMID: 40033224 PMC: 11874639. DOI: 10.1186/s12882-025-04029-y.

References

Yang D, Zhang W, Zhang H, Zhang F, Chen L, Ma L . Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics. Theranostics. 2020; 10(8):3684-3707. PMC: 7069071. DOI: 10.7150/thno.41580. View

Bang Y, Van Cutsem E, Feyereislova A, Chung H, Shen L, Sawaki A . Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376(9742):687-97. DOI: 10.1016/S0140-6736(10)61121-X. View

Sharma P, Hu-Lieskovan S, Wargo J, Ribas A . Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017; 168(4):707-723. PMC: 5391692. DOI: 10.1016/j.cell.2017.01.017. View

Adell M, Migliano S, Upadhyayula S, Bykov Y, Sprenger S, Pakdel M . Recruitment dynamics of ESCRT-III and Vps4 to endosomes and implications for reverse membrane budding. Elife. 2017; 6. PMC: 5665648. DOI: 10.7554/eLife.31652. View

Hanson P, Cashikar A . Multivesicular body morphogenesis. Annu Rev Cell Dev Biol. 2012; 28:337-62. DOI: 10.1146/annurev-cellbio-092910-154152. View

Li X, Wenes M, Romero P, Huang S, Fendt S, Ho P . Navigating metabolic pathways to enhance antitumour immunity and immunotherapy. Nat Rev Clin Oncol. 2019; 16(7):425-441. DOI: 10.1038/s41571-019-0203-7. View

de Araujo Farias V, OValle F, Serrano-Saenz S, Anderson P, Andres E, Lopez-Penalver J . Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci. Mol Cancer. 2018; 17(1):122. PMC: 6094906. DOI: 10.1186/s12943-018-0867-0. View

Sun Y, Liu G, Zhang K, Cao Q, Liu T, Li J . Mesenchymal stem cells-derived exosomes for drug delivery. Stem Cell Res Ther. 2021; 12(1):561. PMC: 8557580. DOI: 10.1186/s13287-021-02629-7. View

Zhou W, Zhou Y, Chen X, Ning T, Chen H, Guo Q . Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment. Biomaterials. 2020; 268:120546. DOI: 10.1016/j.biomaterials.2020.120546. View

10.

Liang L, Zhao L, Wang Y, Wang Y . Treatment for Hepatocellular Carcinoma Is Enhanced When Norcantharidin Is Encapsulated in Exosomes Derived from Bone Marrow Mesenchymal Stem Cells. Mol Pharm. 2021; 18(3):1003-1013. DOI: 10.1021/acs.molpharmaceut.0c00976. View

11.

Jia Z, Zhu H, Sun H, Hua Y, Zhang G, Jiang J . Adipose Mesenchymal Stem Cell-Derived Exosomal microRNA-1236 Reduces Resistance of Breast Cancer Cells to Cisplatin by Suppressing SLC9A1 and the Wnt/β-Catenin Signaling. Cancer Manag Res. 2020; 12:8733-8744. PMC: 7519869. DOI: 10.2147/CMAR.S270200. View

12.

Henne W, Stenmark H, Emr S . Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb Perspect Biol. 2013; 5(9). PMC: 3753708. DOI: 10.1101/cshperspect.a016766. View

13.

Henne W, Buchkovich N, Emr S . The ESCRT pathway. Dev Cell. 2011; 21(1):77-91. DOI: 10.1016/j.devcel.2011.05.015. View

14.

Lee Y, Tan Y, Oon C . Molecular targeted therapy: Treating cancer with specificity. Eur J Pharmacol. 2018; 834:188-196. DOI: 10.1016/j.ejphar.2018.07.034. View

15.

Vietri M, Radulovic M, Stenmark H . The many functions of ESCRTs. Nat Rev Mol Cell Biol. 2019; 21(1):25-42. DOI: 10.1038/s41580-019-0177-4. View

16.

Thery C, Zitvogel L, Amigorena S . Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002; 2(8):569-79. DOI: 10.1038/nri855. View

17.

Zhou J, Ren Y, Tan L, Song X, Wang M, Li Y . Norcantharidin: research advances in pharmaceutical activities and derivatives in recent years. Biomed Pharmacother. 2020; 131:110755. DOI: 10.1016/j.biopha.2020.110755. View

18.

Zhou Y, Zhou W, Chen X, Wang Q, Li C, Chen Q . Bone marrow mesenchymal stem cells-derived exosomes for penetrating and targeted chemotherapy of pancreatic cancer. Acta Pharm Sin B. 2020; 10(8):1563-1575. PMC: 7488356. DOI: 10.1016/j.apsb.2019.11.013. View

19.

Weaver B, Cleveland D . Decoding the links between mitosis, cancer, and chemotherapy: The mitotic checkpoint, adaptation, and cell death. Cancer Cell. 2005; 8(1):7-12. DOI: 10.1016/j.ccr.2005.06.011. View

20.

Schaue D, McBride W . Opportunities and challenges of radiotherapy for treating cancer. Nat Rev Clin Oncol. 2015; 12(9):527-40. PMC: 8396062. DOI: 10.1038/nrclinonc.2015.120. View