Effectiveness of Mesenchymal Stem Cells and Their Derivatives in Modulating Oxidative Stress in Neurodegenerative Diseases: A Structured Narrative Review
Keywords:
Antioxidant signaling, Cell-free therapy, Mitochondrial dysfunction, Neuroinflammation, Nrf2/HO-1 pathway, Reactive oxygen species
Abstract
Background: Oxidative stress plays a critical role in the development and progression of neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). Mesenchymal stem cells (MSCs) and their derivatives have emerged as promising therapeutic strategies due to their antioxidant, anti-inflammatory, and neuroprotective properties. Objective: This review evaluated the effectiveness of MSC-based interventions in modulating oxidative stress in neurodegenerative disease models. Methods: A structured narrative review search was conducted following PRISMA 2020 guidelines using PubMed and Scopus databases for studies published between 2020 and 2025, with the last search in December 2025. Results: 33 studies met the inclusion criteria, primarily involving Parkinson’s and Alzheimer’s disease models. Overall, MSC-based therapies reduced oxidative stress markers, enhanced antioxidant defenses, activated the Nrf2/HO-1 pathway, improved mitochondrial function, and reduced neuroinflammation in experimental neurodegenerative disease models.
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References
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Asemi-Rad, A., Moafi, M., Aliaghaei, A., Abbaszadeh, H.-A., Abdollahifar, M.-A., Ebrahimi, M.-J., Heidari, M. H., & Sadeghi, Y. (n.d.). The effect of dopaminergic neuron transplantation and melatonin coadministration on oxidative stress-induced cell death in Parkinson’s disease. Metabolic Brain, ease,37(8), 2677–2685. https://doi.org/10.1007/s11011-022-01021-5
Barilani, M., Lovejoy, C., Piras, R., Abramov, A. Y., Lazzari, L., & Angelova, P. R. (2022). Age‐related changes in the energy of human mesenchymal stem cells. Journal of Cellular Physiology, 237(3), 1753–1767. https://doi.org/10.1002/jcp.30638
Barkat, mona, El-Agwany, A., Khanfor, A., Kelada, M., Abdel-monsif, D., Dief, A., & Nabil, iman. (2019). The potential therapeutic effect of adipose tissue-derived mesenchymal stem cell transplantation on cuprizone model of multiple sclerosis in the mice. Egyptian Journal of Histology, 0(0), 0–0. https://doi.org/10.21608/ejh.2019.13731.1129
Dabrowska, S., Turano, E., Scambi, I., Virla, F., Nodari, A., Pezzini, F., Galiè, M., Bonetti, B., & Mariotti, R. (2024). A Cellular Model of Amyotrophic Lateral Sclerosis to Study the Therapeutic Effects of Extracellular Vesicles from Adipose Mesenchymal Stem Cells on Microglial Activation. International Journal of Molecular Sciences, 25(11), 5707. https://doi.org/10.3390/ijms25115707
El Mahdy, E. M., Gamal, M., Aboulhoda, B. E., Al Dreny, B. A., Shamaa, A., Rashed, L., Abdallah, A. N. E., & Shamseldeen, A. M. (2023). Amelioration of rotenone-induced Parkinson’s disease; comparing therapeutic role of erythropoietin versus low-level laser activation of mesenchymal stem cells (an in-vivo and in-vitro study). Animal Cells and Systems, 27(1), 272–286. https://doi.org/10.1080/19768354.2023.2273467
Essawy Essawy, A., Abou-ElNaga, O. A., Mehanna, R. A., Badae, N. M., Elsawy, E. S., & Soffar, A. A. (2024). Comparing the effect of intravenous versus intracranial grafting of mesenchymal stem cells against parkinsonism in a rat model: Behavioral, biochemical, pathological and immunohistochemical studies. PLOS ONE, 19(2), e0296297. https://doi.org/10.1371/journal.pone.0296297
Gomez-Sequeda, N., Jimenez-Del-Rio, M., & Velez-Pardo, C. (2024). Combination of Tramiprosate, Curcumin, and SP600125 Reduces the Neuropathological Phenotype in Familial Alzheimer Disease PSEN1 I416T Cholinergic-like Neurons. International Journal of Molecular Sciences, 25(9), 4925. https://doi.org/10.3390/ijms25094925
Gonmanee, T., Petcharat, P., Manprasong, S., Sangkhamanee, S. S., Arayapisit, T., Sritanaudomchai, H., Khwanraj, K., & Dharmasaroja, P. (2025). Human dental pulp stem cell-derived mitochondria restore mitochondrial function and promote neuroregeneration in a cellular model of Parkinson’s disease. Stem Cell Research & Therapy, 16(1), 577. https://doi.org/10.1186/s13287-025-04702-x
Hernández-Pérez, O. R., Juárez-Navarro, K. J., Diaz, N. F., Padilla-Camberos, E., Beltran-Garcia, M. J., Cardenas-Castrejon, D., Corona-Perez, H., Hernández-Jiménez, C., & Díaz-Martínez, N. E. (2022). Biomolecules resveratrol + coenzyme Q10 recover the cell state of human mesenchymal stem cells after 1-methyl-4-phenylpyridinium-induced damage and improve proliferation and neural differentiation. Frontiers in Neuroscience, 16. https://doi.org/10.3389/fnins.2022.929590
Ibrahim, D., Pet, I., Sherkawy, H. S., Eldoumani, H., Fathy, O. M., Elgamal, A., Gharib, H. S. A., Muhammed, A. A., Metwally, A. Sh., Ahmadi, M., Puşcaşiu, D., Abdel-Raheem, S. M., & Abdelfattah-Hassan, A. (2025). Crosstalk between MSC-extracellular vesicles and Olea europaea leaf extract in encapsulated liposomal hydrogel: attenuation of neuroinflammation and brain neurotransmitter and memory impairment associated with obesity-induced high-fat diet. Frontiers in Pharmacology, 16. https://doi.org/10.3389/fphar.2025.1621092
Issa, E. H. B., Alghazo, E. M., Gharaibeh, R., Momani, N. B., Taha, D. Z., Jaradat, R. J., Alzu’bi, A., Almahasneh, F. A., Abu-El-Rub, E., & Al-Zoubi, R. M. (2025). Therapeutic potential and challenges of mesenchymal stem cells in neurological disorders: A concise analysis. Journal of Neuropathology & Experimental Neurology, 84(8), 668–679. https://doi.org/10.1093/jnen/nlaf021
Ji, X., Zhou, S., Wang, N., Wang, J., Wu, Y., Duan, Y., Ni, P., Zhang, J., & Yu, S. (2023). Cerebral-Organoid-Derived Exosomes Alleviate Oxidative Stress and Promote LMX1A-Dependent Dopaminergic Differentiation. International Journal of Molecular Sciences, 24(13), 11048. https://doi.org/10.3390/ijms241311048
Khushi, Kumar, A., Jadhav, K., Gupta, A., & Verma, R. K. (2025). Targeted Delivery of mGluR5 Agonists via Engineered hucMSC-Derived EVs to Enhance Macrophage Function and Mitigate Glutamate-Induced Toxicity. ACS Applied Bio Materials, 8(9), 7728–7742. https://doi.org/10.1021/acsabm.5c00646
Kook, M. G., Lee, S., Shin, N., Kong, D., Kim, D.-H., Kim, M.-S., Kang, H. K., Choi, S. W., & Kang, K.-S. (2020). Repeated intramuscular transplantations of hUCB-MSCs improves motor function and survival in the SOD1 G93A mice through activation of AMPK. Scientific Reports, 10(1), 1572. https://doi.org/10.1038/s41598-020-58221-1
Labunets, I., Toporova, O., Panteleymonova, T., Dovbynchuk, T., Kyryk, V., Kashchuk, O., & Kordium, K. (2025). Comparative effects of human umbilical cord-derived mesenchymal stromal cells and their extracellular vesicles in a mouse model of parkinsonism. Cell and Organ Transplantology, 13(1). https://doi.org/10.22494/cot.v13i1.176
Lei, T., Li, C., Liu, Y., Cui, Z., Deng, S., Cao, J., Yang, H., & Chen, P. (2024). Microfluidics-enabled mesenchymal stem cell derived Neuron like cell membrane coated nanoparticles inhibit inflammation and apoptosis for Parkinson’s Disease. Journal of Nanobiotechnology, 22(1), 370. https://doi.org/10.1186/s12951-024-02587-1
Li, J., Peng, H., Zhang, W., Li, M., Wang, N., Peng, C., Zhang, X., & Li, Y. (2023). Enhanced Nose-to-Brain Delivery of Combined Small Interfering RNAs Using Lesion-Recognizing Nanoparticles for the Synergistic Therapy of Alzheimer’s Disease. ACS Applied Materials & Interfaces, 15(46), 53177–53188. https://doi.org/10.1021/acsami.3c08756
Lin, Y.-H., Lin, K.-L., Wang, X.-W., Lee, J.-J., Wang, F.-S., Wang, P.-W., Lan, M.-Y., Liou, C.-W., & Lin, T.-K. (2024). Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Wharton’s jelly mesenchymal stem cells. Mitochondrion, 76, 101856. https://doi.org/10.1016/j.mito.2024.101856
Ma, S., Ene, J., McGarraugh, C., Ma, S., Esmonde, C., Liu, Y., & Li, Y. (2025). Extracellular Vesicle Secretion from 3D Culture of Human Adipose-Derived Mesenchymal Stem Cells in Scalable Bioreactors. Bioengineering, 12(9), 933. https://doi.org/10.3390/bioengineering12090933
Mateo, J., Suárez-Suárez, M. Á., Fraile, M., Piñera-Parrilla, Á. R., Vizoso, F. J., & Eiro, N. (2025). Secretome from Uterine Cervical Mesenchymal Stem Cells as a Protector of Neuronal Cells Against Oxidative Stress and Inflammation. Biomolecules, 15(10), 1402. https://doi.org/10.3390/biom15101402
Minoia, A., Piritore, F. C., Bolognin, S., Pessoa, J., Bernardes de Jesus, B., Tiso, N., Romanelli, M. G., Schwamborn, J. C., Dalle Carbonare, L., & Valenti, M. T. (2025). Antioxidant, Osteogenic, and Neuroprotective Effects of Homotaurine in Aging and Parkinson’s Disease Models. Antioxidants, 14(3), 249. https://doi.org/10.3390/antiox14030249
Monroe, L., Kaonis, S., Calahan, N., Kabi, N., & Ghosh, S. (2025). Hyperoxia Induced Alteration of Chromatin Structure in Human Bone Marrow Derived Primary Mesenchymal Stromal Cells. Advanced Biology, 9(9). https://doi.org/10.1002/adbi.202400314
Olufunmilayo, E. O., Gerke-Duncan, M. B., & Holsinger, R. M. D. (2023). Oxidative Stress and Antioxidants in Neurodegenerative Disorders. Antioxidants, 12(2), 517. https://doi.org/10.3390/antiox12020517
Provenzano, F., Nyberg, S., Giunti, D., Torazza, C., Parodi, B., Bonifacino, T., Usai, C., Kerlero de Rosbo, N., Milanese, M., Uccelli, A., Shaw, P. J., Ferraiuolo, L., & Bonanno, G. (2022). Micro-RNAs Shuttled by Extracellular Vesicles Secreted from Mesenchymal Stem Cells Dampen Astrocyte Pathological Activation and Support Neuroprotection in In-Vitro Models of ALS. Cells, 11(23), 3923. https://doi.org/10.3390/cells11233923
Puig-Pijuan, T., de Godoy, M. A., Pinheiro Carvalho, L. R., Bodart-Santos, V., Lindoso, R. S., Pimentel-Coelho, P. M., & Mendez-Otero, R. (2020). Human Wharton’s Jelly Mesenchymal Stem Cells Protect Neural Cells from Oxidative Stress Through Paracrine Mechanisms. Future Science OA, 6(9). https://doi.org/10.2144/fsoa-2020-0036
Ramalingam, M., Jeong, H.-S., Hwang, J., Cho, H.-H., Kim, B. C., Kim, E., & Jang, S. (2022). Autophagy Signaling by Neural-Induced Human Adipose Tissue-Derived Stem Cell-Conditioned Medium during Rotenone-Induced Toxicity in SH-SY5Y Cells. International Journal of Molecular Sciences, 23(8), 4193. https://doi.org/10.3390/ijms23084193
Soto-Mercado, V., Mendivil-Perez, M., Velez-Pardo, C., Lopera, F., & Jimenez-Del-Rio, M. (2020). Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer’s disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications. PLOS ONE, 15(5), e0221669. https://doi.org/10.1371/journal.pone.0221669
Soumya, B. S., Gamit, N., Patil, M., Shreenidhi, V. P., Dharmarajan, A., & Warrier, S. (2025). Modeling amyotrophic lateral sclerosis with amniotic membrane-derived mesenchymal stem cells: A novel approach for disease modeling. Experimental Cell Research, 446(1), 114449. https://doi.org/10.1016/j.yexcr.2025.114449
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Published
2026-03-31
How to Cite
Ghanny, N., Pradnyani, P., Salwa, A., Rahajeng, H., Radhina, A., Sari, B., & Baihaki, I. (2026). Effectiveness of Mesenchymal Stem Cells and Their Derivatives in Modulating Oxidative Stress in Neurodegenerative Diseases: A Structured Narrative Review. Indonesian Journal of Life Sciences, 8(01), 132-151. https://doi.org/https://doi.org/10.54250/ijls.v8i01.297
Issue
Section
Cell and Molecular Biology
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