间充质干细胞来源的外泌体在肿瘤治疗中的研究进展
Advances in Mesenchymal Stem Cell-Derived Exosomes in Tumor Therapy
DOI: 10.12677/acm.2024.1451601, PDF,    科研立项经费支持
作者: 王琦玉*：延安大学医学院，陕西 延安；常 乐：陕西省人民医院中心实验室，陕西 西安；徐翠香#：延安大学医学院，陕西 延安；陕西省人民医院中心实验室，陕西 西安
关键词: 间充质干细胞；外泌体；肿瘤治疗；癌症；Mesenchymal Stem Cells； Exosomes； Tumor Therapy； Cancer
摘要: 间充质干细胞(MSCs)是一类来源广泛的多能干细胞，同时具备低免疫原性和高增殖能力的特性，并可从多种组织器官中分离并进行培养。不仅如此，MSCs还能产生大量外泌体(MSCs-exosomes, MSCs-Exo)，其内含有丰富的生物标志物和具有细胞间通信功能的生物分子，从而在免疫调节中发挥着重要作用。在静息或应激条件下，MSCs-Exo可介导肿瘤微环境中细胞间的信息交流和传递。这些特点使其在肿瘤治疗领域的应用前景相当广阔。研究表明，MSCs-Exo在肿瘤的生长、浸润、耐药以及转移等多个方面都具有重要作用。本文综述了MSCs-Exo的定义及特征，着重探讨了MSCs-Exo对肿瘤的影响，以及其在肿瘤治疗领域中的发展与挑战。
Abstract: Mesenchymal stem cells (MSCs) are a widely sourced type of pluripotent stem cell, possessing characteristics of low immunogenicity and high proliferative capacity, and can be isolated and cultured from various tissues and organs. Additionally, MSCs have been found to secrete abundant extracellular vesicles, known as MSCs-exosomes (MSCs-Exo), which contain a rich array of biomolecules and function as intercellular communicators, playing crucial roles in immune regulation. Under both resting and stress conditions, MSCs-Exo mediate intercellular information exchange and transmission within the tumor microenvironment. These features render them promising candidates for applications in cancer therapy. Studies have shown that MSCs-Exo exert significant effects on various aspects of tumor growth, infiltration, drug resistance, and metastasis. This review outlines the definition and characteristics of MSCs-Exo, focusing on their impact on tumors, as well as their development and challenges in the field of cancer therapy.
文章引用：王琦玉, 常乐, 徐翠香. 间充质干细胞来源的外泌体在肿瘤治疗中的研究进展[J]. 临床医学进展, 2024, 14(5): 1662-1669. https://doi.org/10.12677/acm.2024.1451601

参考文献

[1] Shariati, A., Nemati, R., Sadeghipour, Y., et al. (2020) Mesenchymal Stromal Cells (MSCs) for Neurodegenerative Disease: A Promising Frontier. European Journal of Cell Biology, 99, Article ID: 151097. [Google Scholar] [CrossRef] [PubMed]
[2] Tavakoli, S., Ghaderi Jafarbeigloo, H.R., Shariati, A., et al. (2020) Mesenchymal Stromal Cells; a New Horizon in Regenerative Medicine. Journal of Cellular Physiology, 235, 9185-9210. [Google Scholar] [CrossRef] [PubMed]
[3] Markov, A., Thangavelu, L., Aravindhan, S., et al. (2021) Mesenchymal Stem/Stromal Cells as a Valuable Source for the Treatment of Immune-Mediated Disorders. Stem Cell Research & Therapy, 12, Article No. 192. [Google Scholar] [CrossRef] [PubMed]
[4] Lazennec, G. and Lam, P.Y. (2016) Recent Discoveries Concerning the Tumor—Mesenchymal Stem Cell Interactions. Biochimica et Biophysica Acta, 1866, 290-299. [Google Scholar] [CrossRef] [PubMed]
[5] Maumus, M., Jorgensen, C. and Noël, D. (2013) Mesenchymal Stem Cells in Regenerative Medicine Applied to Rheumatic Diseases: Role of Secretome and Exosomes. Biochimie, 95, 2229-2234. [Google Scholar] [CrossRef] [PubMed]
[6] 张娟, 史晋叔, 李剑. 间充质干细胞源性外泌体——未来生物疗法的理想载体[J]. 中国实验血液学杂志, 2015, 23(4): 1179-1183.
[7] 赵贵芳. 脐带间充质干细胞及其来源外泌体修复皮肤损伤的机制研究[D]: [博士学位论文]. 长春: 吉林大学, 2016.
[8] Ren, Z., Qi, Y., Sun, S., et al. (2020) Mesenchymal Stem Cell-Derived Exosomes: Hope for Spinal Cord Injury Repair. Stem Cells and Development, 29, 1467-1478. [Google Scholar] [CrossRef] [PubMed]
[9] Bao, C. and He, C. (2021) The Role and Therapeutic Potential of MSC-Derived Exosomes in Osteoarthritis. Archives of Biochemistry and Biophysics, 710, Article ID: 109002. [Google Scholar] [CrossRef] [PubMed]
[10] Lai, R.C., Arslan, F., Lee, M.M., et al. (2010) Exosome Secreted by MSC Reduces Myocardial Ischemia/Reperfusion Injury. Stem Cell Research, 4, 214-222. [Google Scholar] [CrossRef] [PubMed]
[11] Harding, C., Heuser, J. and Stahl, P. (1983) Receptor-Mediated Endocytosis of Transferrin and Recycling of the Transferrin Receptor in Rat Reticulocytes. Journal of Cell Biology, 97, 329-339. [Google Scholar] [CrossRef] [PubMed]
[12] Johnstone, R.M., Adam, M., Hammond, J.R., et al. (1987) Vesicle Formation during Reticulocyte Maturation. Association of Plasma Membrane Activities with Released Vesicles (Exosomes). Journal of Biological Chemistry, 262, 9412-9420. [Google Scholar] [CrossRef] 
[13] Vlassov, A.V., Magdaleno, S., Setterquist, R., et al. (2012) Exosomes: Current Knowledge of Their Composition, Biological Functions, and Diagnostic and Therapeutic Potentials. Biochimica et Biophysica Acta, 1820, 940-948. [Google Scholar] [CrossRef] [PubMed]
[14] Heo, J.S., Choi, Y., Kim, H.S., et al. (2016) Comparison of Molecular Profiles of Human Mesenchymal Stem Cells Derived from Bone Marrow, Umbilical Cord Blood, Placenta and Adipose Tissue. International Journal of Molecular Medicine, 37, 115-125. [Google Scholar] [CrossRef] [PubMed]
[15] Meyer, M.B., Benkusky, N.A., Sen, B., et al. (2016) Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-Derived Mesenchymal Stem Cells. Journal of Biological Chemistry, 291, 17829-17847. [Google Scholar] [CrossRef] 
[16] Hass, R. (2020) Role of MSC in the Tumor Microenvironment. Cancers (Basel), 12, Article No. 2107. [Google Scholar] [CrossRef] [PubMed]
[17] Timaner, M., Tsai, K.K. and Shaked, Y. (2020) The Multifaceted Role of Mesenchymal Stem Cells in Cancer. Seminars in Cancer Biology, 60, 225-237. [Google Scholar] [CrossRef] [PubMed]
[18] Yang, M., Lin, J., Tang, J., et al. (2020) Decreased Immunomodulatory and Secretory Capability of Aging Human Umbilical Cord Mesenchymal Stem Cells in Vitro. Biochemical and Biophysical Research Communications, 525, 633-638. [Google Scholar] [CrossRef] [PubMed]
[19] Phinney, D.G. and Prockop, D.J. (2007) Concise Review: Mesenchymal Stem/Multipotent Stromal Cells: The State of Transdifferentiation and Modes of Tissue Repair—Current Views. Stem Cells, 25, 2896-2902. [Google Scholar] [CrossRef] [PubMed]
[20] Shao, H., Im, H., Castro, C.M., et al. (2018) New Technologies for Analysis of Extracellular Vesicles. Chemical Reviews, 118, 1917-1950. [Google Scholar] [CrossRef] [PubMed]
[21] Vakhshiteh, F., Atyabi, F. and Ostad, S.N. (2019) Mesenchymal Stem Cell Exosomes: A Two-Edged Sword in Cancer Therapy. International Journal of Nanomedicine, 14, 2847-2859. [Google Scholar] [CrossRef] 
[22] Pan, B.T. and Johnstone, R.M. (1983) Fate of the Transferrin Receptor during Maturation of Sheep Reticulocytes in Vitro: Selective Externalization of the Receptor. Cell, 33, 967-978. [Google Scholar] [CrossRef] [PubMed]
[23] Simpson, R.J., Jensen, S.S. and Lim, J.W. (2008) Proteomic Profiling of Exosomes: Current Perspectives. Proteomics, 8, 4083-4099. [Google Scholar] [CrossRef] [PubMed]
[24] Christianson, H.C., Svensson, K.J., Van Kuppevelt, T.H., et al. (2013) Cancer Cell Exosomes Depend on Cell-Surface Heparan Sulfate Proteoglycans for Their Internalization and Functional Activity. Proceedings of the National Academy of Sciences of the United States of America, 110, 17380-17385. [Google Scholar] [CrossRef] [PubMed]
[25] Pegtel, D.M. and Gould, S.J. (2019) Exosomes. Annual Review of Biochemistry, 88, 487-514. [Google Scholar] [CrossRef] [PubMed]
[26] Chen, B., Li, Q., Zhao, B., et al. (2017) Stem Cell-Derived Extracellular Vesicles as a Novel Potential Therapeutic Tool for Tissue Repair. Stem Cells Translational Medicine, 6, 1753-1758. [Google Scholar] [CrossRef] [PubMed]
[27] Liang, Y., Zhang, D., Li, L., et al. (2020) Exosomal MicroRNA-144 from Bone Marrow-Derived Mesenchymal Stem Cells Inhibits the Progression of Non-Small Cell Lung Cancer by Targeting CCNE1 and CCNE2. Stem Cell Research & Therapy, 11, Article No. 87. [Google Scholar] [CrossRef] [PubMed]
[28] Luo, M., Wu, C., Guo, E., et al. (2019) FOXO3a Knockdown Promotes Radioresistance in Nasopharyngeal Carcinoma by Inducing Epithelial-Mesenchymal Transition and the Wnt/β-Catenin Signaling Pathway. Cancer Letters, 455, 26-35. [Google Scholar] [CrossRef] [PubMed]
[29] Lee, J.K., Park, S.R., Jung, B.K., et al. (2013) Exosomes Derived from Mesenchymal Stem Cells Suppress Angiogenesis by Down-Regulating VEGF Expression in Breast Cancer Cells. PLOS ONE, 8, e84256. [Google Scholar] [CrossRef] [PubMed]
[30] Qiu, L., Wang, J., Chen, M., et al. (2020) Exosomal MicroRNA‑146a Derived from Mesenchymal Stem Cells Increases the Sensitivity of Ovarian Cancer Cells to Docetaxel and Taxane via a LAMC2‑Mediated PI3K/Akt Axis. International Journal of Molecular Medicine, 46, 609-620. [Google Scholar] [CrossRef] [PubMed]
[31] Zhou, Y., Zhou, W., Chen, X., et al. (2020) Bone Marrow Mesenchymal Stem Cells-Derived Exosomes for Penetrating and Targeted Chemotherapy of Pancreatic Cancer. Acta Pharmaceutica Sinica B, 10, 1563-1575. [Google Scholar] [CrossRef] [PubMed]
[32] Katakowski, M., Buller, B., Zheng, X., et al. (2013) Exosomes from Marrow Stromal Cells Expressing MiR-146b Inhibit Glioma Growth. Cancer Letters, 335, 201-204. [Google Scholar] [CrossRef] [PubMed]
[33] Takahara, K., Ii, M., Inamoto, T., et al. (2016) MicroRNA-145 Mediates the Inhibitory Effect of Adipose Tissue-Derived Stromal Cells on Prostate Cancer. Stem Cells and Development, 25, 1290-1298. [Google Scholar] [CrossRef] [PubMed]
[34] Li, X. and Li, Z. (2019) Effects of Human Umbilical Cord Mesenchymal Stem Cells on Co-Cultured Ovarian Carcinoma Cells. Microscopy Research and Technique, 82, 898-902. [Google Scholar] [CrossRef] [PubMed]
[35] Lin, R., Wang, S. and Zhao, R.C. (2013) Exosomes from Human Adipose-Derived Mesenchymal Stem Cells Promote Migration through Wnt Signaling Pathway in a Breast Cancer Cell Model. Molecular and Cellular Biochemistry, 383, 13-20. [Google Scholar] [CrossRef] [PubMed]
[36] Wan, F.Z., Chen, K.H., Sun, Y.C., et al. (2020) Exosomes Overexpressing MiR-34c Inhibit Malignant Behavior and Reverse the Radioresistance of Nasopharyngeal Carcinoma. Journal of Translational Medicine, 18, Article No. 12. [Google Scholar] [CrossRef] [PubMed]
[37] Jahangiri, B., Khalaj-Kondori, M., Asadollahi, E., et al. (2022) MSC-Derived Exosomes Suppress Colorectal Cancer Cell Proliferation and Metastasis via MiR-100/MTOR/MiR-143 Pathway. International Journal of Pharmaceutics, 627, Article ID: 122214. [Google Scholar] [CrossRef] [PubMed]
[38] Xu, Y., Lai, Y., Cao, L., et al. (2021) Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomal MicroRNA-451a Represses Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Inhibiting ADAM10. RNA Biology, 18, 1408-1423. [Google Scholar] [CrossRef] [PubMed]
[39] Zheng, P., Chen, L., Yuan, X., et al. (2017) Exosomal Transfer of Tumor-Associated Macrophage-Derived MiR-21 Confers Cisplatin Resistance in Gastric Cancer Cells. Journal of Experimental & Clinical Cancer Research, 36, Article No. 53. [Google Scholar] [CrossRef] [PubMed]
[40] Luo, T., Liu, Q., Tan, A., et al. (2020) Mesenchymal Stem Cell-Secreted Exosome Promotes Chemoresistance in Breast Cancer via Enhancing MiR-21-5p-Mediated S100A6 Expression. Molecular Therapy—Oncolytics, 19, 283-293. [Google Scholar] [CrossRef] [PubMed]
[41] Kim, M.S., Haney, M.J., Zhao, Y., et al. (2018) Engineering Macrophage-Derived Exosomes for Targeted Paclitaxel Delivery to Pulmonary Metastases: In Vitro and in Vivo Evaluations. Nanomedicine, 14, 195-204. [Google Scholar] [CrossRef] [PubMed]
[42] Lou, G., Chen, Z., Zheng, M., et al. (2017) Mesenchymal Stem Cell-Derived Exosomes as a New Therapeutic Strategy for Liver Diseases. Experimental & Molecular Medicine, 49, E346. [Google Scholar] [CrossRef] [PubMed]
[43] Smyth, T.J., Redzic, J.S., Graner, M.W., et al. (2014) Examination of the Specificity of Tumor Cell Derived Exosomes with Tumor Cells in Vitro. Biochimica et Biophysica Acta, 1838, 2954-2965. [Google Scholar] [CrossRef] [PubMed]
[44] Bashyal, S., Thapa, C. and Lee, S. (2022) Recent Progresses in Exosome-Based Systems for Targeted Drug Delivery to the Brain. Journal of Controlled Release, 348, 723-744. [Google Scholar] [CrossRef] [PubMed]
[45] Vader, P., Mol, E.A., Pasterkamp, G., et al. (2016) Extracellular Vesicles for Drug Delivery. Advanced Drug Delivery Reviews, 106, 148-156. [Google Scholar] [CrossRef] [PubMed]
[46] Liu, H., Deng, S., Han, L., et al. (2022) Mesenchymal Stem Cells, Exosomes and Exosome-Mimics as Smart Drug Carriers for Targeted Cancer Therapy. Colloids and Surfaces B: Biointerfaces, 209, Article ID: 112163. [Google Scholar] [CrossRef] [PubMed]
[47] Zhou, W., Zhou, Y., Chen, X., et al. (2021) Pancreatic Cancer-Targeting Exosomes for Enhancing Immunotherapy and Reprogramming Tumor Microenvironment. Biomaterials, 268, Article ID: 120546. [Google Scholar] [CrossRef] [PubMed]

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