Review: Wharton’s Jelly MSCs Secretome as a Neurodegenerative Therapeutic Approach
Iis Nur Azizah(1), Muhammad Novrizal Abdi Sahid(2), Retno Murwanti(3*)
(1) Master of Pharmaceutical Science, Faculty of Pharmacy, Universitas Gadjah Mada
(2) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada
(3) Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy
(*) Corresponding Author
Abstract
Wharton’s Jelly Mesenchymal Stem Cells (WJMSCs) have great potential in regenerative therapy, mainly because their secretome is rich in bioactive molecules. WJMSCs secretome plays a role in the treatment of various neurodegenerative diseases, such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). This journal review aims to analyze the therapeutic potential of Wharton’s Jelly Mesenchymal Stem Cells (WJMSCs) secretome in treating various neurodegenerative diseases. Literature searches were conducted through electronic databases such as Elsevier, Google Scholar, PubMed, Science Direct, and Springer Link. Based on the review conducted, data obtained that in AD, this secretome reduces oxidative stress, increases neurogenesis, and inhibits β-amyloid toxicity. In PD, WJMSCs protect dopaminergic neurons, increase dopamine levels, and improve motor function. For ALS, WJMSCs secretome reduced inflammation and increased neurotrophic factors, while MS supported remyelination and neuroprotection. With these benefits, WJMSC secretome has the potential to be an innovative therapy for neurodegenerative diseases, although further clinical studies are needed.
Keywords
Full Text:
PDFReferences
Angeloni, C., Gatti, M., Prata, C., Hrelia, S., & Maraldi, T. (2020). Role of Mesenchymal Stem Cells in Counteracting Oxidative Stress—Related Neurodegeneration. International Journal of Molecular Sciences, 21(9), 3299. https://doi.org/10.3390/ijms21093299
Ardianto, C., Shen, R., Barus, J. F. A., Sasmita, P. K., Turana, Y., Lilis, L., & Sidharta, V. M. (2022). Secretome as neuropathology-targeted intervention of Parkinson’s disease. Regenerative Therapy, 21, 288–293. https://doi.org/10.1016/j.reth.2022.08.003
Ayeni, E. A., Aldossary, A. M., Ayejoto, D. A., Gbadegesin, L. A., Alshehri, A. A., Alfassam, H. A., Afewerky, H. K., Almughem, F. A., Bello, S. M., & Tawfik, E. A. (2022). Neurodegenerative Diseases: Implications of Environmental and Climatic Influences on Neurotransmitters and Neuronal Hormones Activities. International Journal of Environmental Research and Public Health, 19(19), 12495. https://doi.org/10.3390/ijerph191912495
Bodart-Santos, V., de Carvalho, L. R. P., de Godoy, M. A., Batista, A. F., Saraiva, L. M., Lima, L. G., Abreu, C. A., De Felice, F. G., Galina, A., Mendez-Otero, R., & Ferreira, S. T. (2019). Extracellular vesicles derived from human Wharton’s jelly mesenchymal stem cells protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers. Stem Cell Research & Therapy, 10, 332. https://doi.org/10.1186/s13287-019-1432-5
Chen, P., Tang, S., Gao, H., Zhang, H., Chen, C., Fang, Z., Peng, G., Weng, H., Chen, A., Zhang, C., Qiu, Z., Li, S., Chen, J., Chen, L., & Chen, X. (2022). Wharton’s jelly mesenchymal stem cell-derived small extracellular vesicles as natural nanoparticles to attenuate cartilage injury via microRNA regulation. International Journal of Pharmaceutics, 623, 121952. https://doi.org/10.1016/j.ijpharm.2022.121952
Drobiova, H., Sindhu, S., Ahmad, R., Haddad, D., Al-Mulla, F., & Al Madhoun, A. (2023). Wharton’s jelly mesenchymal stem cells: A concise review of their secretome and prospective clinical applications. Frontiers in Cell and Developmental Biology, 11, 1211217. https://doi.org/10.3389/fcell.2023.1211217
Erta, M., Quintana, A., & Hidalgo, J. (2012). Interleukin-6, a Major Cytokine in the Central Nervous System. International Journal of Biological Sciences, 8(9), 1254–1266. https://doi.org/10.7150/ijbs.4679
Fatihaturahmi, F., Yuliana, Y., & Yulastri, A. (2023). Literature Review: Penyakit Degeneratif : Penyebab, Akibat, Pencegahan Dan Penanggulangan. JGK: Jurnal Gizi Dan Kesehatan, 3(1), Article 1. https://doi.org/10.36086/jgk.v3i1.1535
Foo, J. B., Looi, Q. H., Chong, P. P., Hassan, N. H., Yeo, G. E. C., Ng, C. Y., Koh, B., How, C. W., Lee, S. H., & Law, J. X. (2021). Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine. Stem Cells International, 2021, 1–30. https://doi.org/10.1155/2021/2616807
Garcia-Contreras, M., & Thakor, A. S. (2021). Human adipose tissue-derived mesenchymal stem cells and their extracellular vesicles modulate lipopolysaccharide activated human microglia. Cell Death Discovery, 7(1), 1–13. https://doi.org/10.1038/s41420-021-00471-7
Ghasemi, M., Roshandel, E., Mohammadian, M., Farhadihosseinabadi, B., Akbarzadehlaleh, P., & Shamsasenjan, K. (2023). Mesenchymal stromal cell-derived secretome-based therapy for neurodegenerative diseases: Overview of clinical trials. Stem Cell Research & Therapy, 14(1), 122. https://doi.org/10.1186/s13287-023-03264-0
González-Fernández, C., González, P., & Rodríguez, F. J. (2020). New insights into Wnt signaling alterations in amyotrophic lateral sclerosis: A potential therapeutic target? Neural Regeneration Research, 15(9), 1580–1589. https://doi.org/10.4103/1673-5374.276320
González-González, A., García-Sánchez, D., Dotta, M., Rodríguez-Rey, J. C., & Pérez-Campo, F. M. (2020). Mesenchymal stem cells secretome: The cornerstone of cell-free regenerative medicine. World Journal of Stem Cells, 12(12), 1529–1552. https://doi.org/10.4252/wjsc.v12.i12.1529
Govindarajulu, M., Pinky, P. D., Bloemer, J., Ghanei, N., Suppiramaniam, V., & Amin, R. (2018). Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer’s Disease. PPAR Research, 2018, 2010675. https://doi.org/10.1155/2018/2010675
Gugliandolo, A., Bramanti, P., & Mazzon, E. (2020). Mesenchymal Stem Cells in Multiple Sclerosis: Recent Evidence from Pre-Clinical to Clinical Studies. International Journal of Molecular Sciences, 21(22), 8662. https://doi.org/10.3390/ijms21228662
Harrell, C. R., Volarevic, A., & Volarevic, V. (2022). Therapeutic Effects of Mesenchymal Stem Cells on Cognitive Deficits. In K. H. Haider (Ed.), Handbook of Stem Cell Therapy (pp. 413–436). Springer Nature. https://doi.org/10.1007/978-981-19-2655-6_15
Hoang, D. M., Pham, P. T., Bach, T. Q., Ngo, A. T. L., Nguyen, Q. T., Phan, T. T. K., Nguyen, G. H., Le, P. T. T., Hoang, V. T., Forsyth, N. R., Heke, M., & Nguyen, L. T. (2022). Stem cell-based therapy for human diseases. Signal Transduction and Targeted Therapy, 7(1), 272. https://doi.org/10.1038/s41392-022-01134-4
Jalali, M. S., Sarkaki, A., Farbood, Y., Azandeh, S. S., Mansouri, E., Ghasemi Dehcheshmeh, M., & Saki, G. (2020). Transplanted Wharton’s jelly mesenchymal stem cells improve memory and brain hippocampal electrophysiology in rat model of Parkinson’s disease. Journal of Chemical Neuroanatomy, 110, 101865. https://doi.org/10.1016/j.jchemneu.2020.101865
Jalali, M. S., Sarkaki, A., Farbood, Y., Azandeh, S. S., Mansouri, E., Ghasemi Dehcheshmeh, M., & Saki, G. (2021). Neuroprotective effects of Wharton’s jelly-derived mesenchymal stem cells on motor deficits due to Parkinson’s disease. Iranian Journal of Basic Medical Sciences, 24(9), 1173–1181. https://doi.org/10.22038/IJBMS.2021.54091.12159
Janalipour, K. (2019). Multiple sclerosis symptoms. In Neurological Disorders and Imaging Physics, Volume 2: Engineering and clinical perspectives of multiple sclerosis (pp. 123–154). Scopus. https://doi.org/10.1088/978-0-7503-1762-7ch5
Kalamegam, G., Sait, K. H. W., Ahmed, F., Kadam, R., Pushparaj, P. N., Anfinan, N., Rasool, M., Jamal, M. S., Abu-Elmagd, M., & Al-Qahtani, M. (2018). Human Wharton’s Jelly Stem Cell (hWJSC) Extracts Inhibit Ovarian Cancer Cell Lines OVCAR3 and SKOV3 in vitro by Inducing Cell Cycle Arrest and Apoptosis. Frontiers in Oncology, 8, 592. https://doi.org/10.3389/fonc.2018.00592
Kim, D.-W., Staples, M., Shinozuka, K., Pantcheva, P., Kang, S.-D., & Borlongan, C. (2013). Wharton’s Jelly-Derived Mesenchymal Stem Cells: Phenotypic Characterization and Optimizing Their Therapeutic Potential for Clinical Applications. International Journal of Molecular Sciences, 14(6), 11692–11712. https://doi.org/10.3390/ijms140611692
Konala, V. B. R., Bhonde, R., & Pal, R. (2020). Secretome studies of mesenchymal stromal cells (MSCs) isolated from three tissue sources reveal subtle differences in potency. In Vitro Cellular & Developmental Biology - Animal, 56(9), 689–700. https://doi.org/10.1007/s11626-020-00501-1
Marconi, S., Bonaconsa, M., Scambi, I., Squintani, G. M., Rui, W., Turano, E., Ungaro, D., D’Agostino, S., Barbieri, F., Angiari, S., Farinazzo, A., Constantin, G., Carro, U. D., Bonetti, B., & Mariotti, R. (2013). Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model. Neuroscience, 248, 333–343. https://doi.org/10.1016/j.neuroscience.2013.05.034
Marcus, A. J., & Woodbury, D. (2008). Fetal stem cells from extra-embryonic tissues: Do not discard. Journal of Cellular and Molecular Medicine, 12(3), 730–742. https://doi.org/10.1111/j.1582-4934.2008.00221.x
Mukai, T., Tojo, A., & Nagamura-Inoue, T. (2018). Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation. Frontiers in Neurology, 9. https://doi.org/10.3389/fneur.2018.00466
Piscopo, P., Bellenghi, M., Manzini, V., Crestini, A., Pontecorvi, G., Corbo, M., Ortona, E., Carè, A., & Confaloni, A. (2021). A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers. International Journal of Molecular Sciences, 22(9), 4423. https://doi.org/10.3390/ijms22094423
Putri, N. P., Ali, H., Tofrizal, T., Darwin, E., Susanti, R., & Hasmiwati, H. (2023). Pengaruh Pemberian Mesenchymal Stem Cells Wharton’s Jelly terhadap Ekspresi Gen PPAR-γ pada Tikus Alzheimer. Jurnal Kesehatan Andalas, 12(2), 70. https://doi.org/10.25077/jka.v12i2.2142
Salwierak-Głośna, K., Piątek, P., Domowicz, M., & Świderek-Matysiak, M. (2022). Effect of Multiple Sclerosis Cerebrospinal Fluid and Oligodendroglia Cell Line Environment on Human Wharton’s Jelly Mesenchymal Stem Cells Secretome. International Journal of Molecular Sciences, 23(4), 2177. https://doi.org/10.3390/ijms23042177
Sandonà, M., Di Pietro, L., Esposito, F., Ventura, A., Silini, A. R., Parolini, O., & Saccone, V. (2021). Mesenchymal Stromal Cells and Their Secretome: New Therapeutic Perspectives for Skeletal Muscle Regeneration. Frontiers in Bioengineering and Biotechnology, 9, 652970. https://doi.org/10.3389/fbioe.2021.652970
Semenov, O. V., Koestenbauer, S., Riegel, M., Zech, N., Zimmermann, R., Zisch, A. H., & Malek, A. (2010). Multipotent mesenchymal stem cells from human placenta: Critical parameters for isolation and maintenance of stemness after isolation. American Journal of Obstetrics and Gynecology, 202(2), 193.e1-193.e13. https://doi.org/10.1016/j.ajog.2009.10.869
Siokas, V., Aloizou, A.-M., Pateraki, G., Liampas, I., Mitsias, P. D., Bogdanos, D. P., & Dardiotis, E. (2021). Chapter 21—Toxicology of neurodegenerative diseases. In A. M. Tsatsakis (Ed.), Toxicological Risk Assessment and Multi-System Health Impacts from Exposure (pp. 247–258). Academic Press. https://doi.org/10.1016/B978-0-323-85215-9.00048-9
Su, Y., Xu, C., Cheng, W., Zhao, Y., Sui, L., & Zhao, Y. (2023). Pretreated Mesenchymal Stem Cells and Their Secretome: Enhanced Immunotherapeutic Strategies. International Journal of Molecular Sciences, 24(2), 1277. https://doi.org/10.3390/ijms24021277
Taherian, M., Bayati, P., & Mojtabavi, N. (2024). Stem cell-based therapy for fibrotic diseases: Mechanisms and pathways. Stem Cell Research & Therapy, 15(1), 170. https://doi.org/10.1186/s13287-024-03782-5
Tang, J., Kang, Y., Zhou, Y., Chen, Q., Lan, J., Liu, X., & Peng, Y. (2023). Umbilical cord mesenchymal stem cell-conditioned medium inhibits microglial activation to ameliorate neuroinflammation in amyotrophic lateral sclerosis mice and cell models. Brain Research Bulletin, 202, 110760. https://doi.org/10.1016/j.brainresbull.2023.110760
Tang, Y., Zhou, Y., & Li, H.-J. (2021). Advances in mesenchymal stem cell exosomes: A review. Stem Cell Research & Therapy, 12, 71. https://doi.org/10.1186/s13287-021-02138-7
Teixeira, F. G., Carvalho, M. M., Panchalingam, K. M., Rodrigues, A. J., Mendes‐Pinheiro, B., Anjo, S., Manadas, B., Behie, L. A., Sousa, N., & Salgado, A. J. (2017). Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal Behavior in a Rat Model of Parkinson’s Disease. Stem Cells Translational Medicine, 6(2), 634–646. https://doi.org/10.5966/sctm.2016-0071
Tesco, G., & Lomoio, S. (2022). Pathophysiology of neurodegenerative diseases: An interplay among axonal transport failure, oxidative stress, and inflammation? Seminars in Immunology, 59, 101628. https://doi.org/10.1016/j.smim.2022.101628
Yasuhara, T., Shingo, T., Kobayashi, K., Takeuchi, A., Yano, A., Muraoka, K., Matsui, T., Miyoshi, Y., Hamada, H., & Date, I. (2004). Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson’s disease. European Journal of Neuroscience, 19(6), 1494–1504. https://doi.org/10.1111/j.1460-9568.2004.03254.x
Zavatti, M., Gatti, M., Beretti, F., Palumbo, C., & Maraldi, T. (2022). Exosomes Derived from Human Amniotic Fluid Mesenchymal Stem Cells Preserve Microglia and Neuron Cells from Aβ. International Journal of Molecular Sciences, 23(9), 4967. https://doi.org/10.3390/ijms23094967
Zhdanova, D. Yu., Poltavtseva, R. A., Svirshchevskaya, E. V., & Bobkova, N. V. (2021). Effect of Intranasal Administration of Multipotent Mesenchymal Stromal Cell Exosomes on Memory of Mice in Alzheimer’s Disease Model. Bulletin of Experimental Biology and Medicine, 170(4), 575–582. https://doi.org/10.1007/s10517-021-05109-3
Zhidu, S., Ying, T., Rui, J., & Chao, Z. (2024). Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: Challenges and opportunities. Stem Cell Research & Therapy, 15(1), 266. https://doi.org/10.1186/s13287-024-03885-z
Article Metrics
Refbacks
- There are currently no refbacks.
Faculty of Pharmacy
Universitas Gadjah Mada







