Neurodegenerative Diseases

Neurodegenerative Diseases

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In recent years, there has been significant interest in determining the role of stem cell therapies in various neurodegenerative diseases. While there is still much work to be done in this area, there is potential for stem cells to offer a cure for these diseases. In particular, stem cells can regenerate tissue and repair damage. Through the targeted application of stem cells at the point of treatment, they can differentiate into beneficial, regenerative cells, potentially treating diseases like Alzheimer’s, Parkinson’s, and multiple sclerosis. While there is still much work to be done in this area, the potential for stem cells to offer a cure for these diseases is very exciting.

In recent years, there has been significant interest in determining the role of stem cell therapies in various neurodegenerative diseases. Various in vitro and animal model studies (1) have confirmed the following properties of different types of stem cells: formation of new myelin, prolongation of neuronal vitality, reduction of oxidative stress, immunomodulation, and formation of new blood vessels, all of which translate into neuroprotection (2,3).

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Although it is necessary to strengthen further the evidence on safety/efficacy, cell type, dosage, routes of administration, etc., the currently available information and data show tolerability and delayed progression of diseases, including multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson’s disease (4-17).

The treatment of multiple sclerosis (MS) based on regenerative medicine has developed such a strong foundation of evidence that the American Society for Blood and Marrow Transplantation has recently recommended including severe forms of MS among the indications for autologous hematopoietic stem cell transplantation (18). A recent systematic review found that 70% of patients with MS showed disease stabilization after the administration of stem cells (19). With this, the academic and scientific world has opened the door for clinical studies to explore the roles of other types of stem cells, such as those from Wharton’s jelly or the umbilical cord, whose safety of intrathecal administration has already been documented (8).

Parkinson’s disease (PD) results from the progressive loss of neurons in specific brain regions. The current treatment approach consists of improving symptoms with medications or neurosurgery but not preventing damage to the neurons involved, meaning that greater neuroprotective strategies must be developed (20).

The ability of stem cells to repair the damage caused by PD has been demonstrated in vitro. Studies on the safety and efficacy of stem cell treatment in animal models of PD are conclusive, so research in humans has been authorized. Thus far, the clinical evidence can be summarized as follows: i) Safety studies of their application in humans leave no doubt: stem cells are a therapeutic tool with a meager rate of undesirable effects and are not associated with severe adverse effects. ii) Although not yet decisive, efficacy studies’ evidence is becoming more robust. Stem cells are emerging as a therapy for improving the patient’s clinical condition, radiological imaging features, and neuropsychological scores. (21-27).

Regarding the role of stem cells in Alzheimer’s disease, there is an excellent theoretical claim for a potential benefit (16,28). Some studies in animal models confirm this (29), while the evidence in humans is limited but very promising (30-34).


1. Zhou Q, Yuan M, Qiu W, Cao W, Xu R. Preclinical studies of mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: a systemic review and metaanalysis. Neurol Sci. 2021. doi: 10.1007/s10072-020-05036-7.
2. Abbasi-Kangevari M, Ghamari SH, Safaeinejad F, Bahrami S, Niknejad H. Potential Therapeutic Features of Human Amniotic Mesenchymal Stem Cells in Multiple Sclerosis: Immunomodulation, Inflammation Suppression, Angiogenesis Promotion, Oxidative Stress Inhibition, Neurogenesis Induction, MMPs Regulation, and Remyelination Stimulation. Front Immunol. 2019;10:238. doi: 10.3389/fimmu.2019.00238.
3. Gruchot J, Weyers V, Göttle P, Förster M, Hartung HP, Küry P, et al. The Molecular Basis for Remyelination Failure in Multiple Sclerosis. Cells. 2019;8(8). pii: E825. doi: 10.3390/cells8080825.
4. Mansoor SR, Zabihi E, Ghasemi-Kasman M. The potential use of mesenchymal stem cells for the treatment of multiple sclerosis. Life Sci. 2019;235:116830. doi: 10.1016/j.lfs.2019.116830.
5. Tolf A, Fagius J, Carlson K, Åkerfeldt T, Granberg T, Larsson EM, Burman J. Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation. Acta Neurol Scand. 2019;140(5):320-327. doi: 10.1111/ane.13147.
6. Ruiz-Argüelles GJ, Olivares-Gazca JC, Olivares-Gazca M, Leon-Peña AA, Murrieta-Alvarez I, Cantero-Fortiz Y, et al. Self-reported changes in the expanded disability status scale score in patients with multiple sclerosis after autologous stem cell transplants: real-world data from a single center. Clin Exp Immunol. 2019;198(3):351-358. doi: 10.1111/cei.13358. 7. Berry JD, Cudkowicz ME, Windebank AJ, Staff NP, Owegi M, Nicholson K, et al. NurOwn, phase 2, randomized, clinical trial in patients with ALS: Safety, clinical, and biomarker results. Neurology. 2019;93(24):e2294-e2305. doi: 10.1212/WNL.0000000000008620.
8. Nabavi SM, Arab L, Jarooghi N, Bolurieh T, Abbasi F, Mardpour S, et al. Safety, Feasibility of Intravenous and Intrathecal Injection of Autologous Bone Marrow Derived Mesenchymal Stromal Cells in Patients with Amyotrophic Lateral Sclerosis: An Open Label Phase I Clinical Trial. Cell J. 2019;20(4):592-598. doi: 10.22074/cellj.2019.5370.
9. Barczewska M, Grudniak M, Maksymowicz S, Siwek T, Ołdak T, Jezierska-Woźniak K, et al. Safety of intrathecal injection of Wharton’s jelly-derived mesenchymal stem cells in amyotrophic lateral sclerosis therapy. Neural Regen Res. 2019;14(2):313-318. doi: 10.4103/1673-5374.243723.
10. Gugliandolo A, Bramanti P, Mazzon E. Mesenchymal Stem Cells: A Potential Therapeutic Approach for Amyotrophic Lateral Sclerosis? Stem Cells Int. 2019;3675627. doi: 10.1155/2019/3675627.
11. Jafarzadeh Bejargafshe M, Hedayati M, Zahabiasli S, Tahmasbpour E, Rahmanzadeh S, Nejad-Moghaddam A. Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis. Stem Cell Investig. 2019;6:44. doi: 10.21037/sci.2019.10.06.
12. Oliveira AG, Gonçalves M, Ferreira H, M Neves N. Growing evidence supporting the use of mesenchymal stem cell therapies in multiple sclerosis: A systematic review. Mult Scler Relat Disord. 2019;38:101860. doi:10.1016/j.msard.2019.101860.
13. Zhou Y, Zhang X, Xue H, Liu L, Zhu J, Jin T. Autologous Mesenchymal Stem Cell Transplantation in Multiple Sclerosis: A Meta-Analysis. Stem Cells Int. 2019;2019:8536785. doi: 10.1155/2019/8536785.
14. Chen JJ. Overview of current and emerging therapies for amytrophic lateral sclerosis. Am J Manag Care. 2020;26(9 Suppl):S191-S197. doi: 10.37765/ajmc.2020.88483.
15. Siwek T, Jezierska-Woźniak K, Maksymowicz S, Barczewska M, Sowa M, Badowska W, et al. Repeat Administration of Bone Marrow-Derived Mesenchymal Stem Cells for Treatment of Amyotrophic Lateral Sclerosis. Med Sci Monit. 2020;26:e927484. doi: 10.12659/MSM.927484.
16. Barati S, Tahmasebi F, Faghihi F. Effects of mesenchymal stem cells transplantation on multiple sclerosis patients. Neuropeptides. 2020;84:102095. doi: 10.1016/j.npep.2020.102095.
17. Ebrahimi T, Abasi M, Seifar F, Eyvazi S, Hejazi MS, Tarhriz V, et al. Transplantation of Stem Cells as a Potential Therapeutic Strategy in Neurodegenerative Disorders. Curr Stem Cell Res Ther. 2020. doi: 10.2174/1574888X15666200628141314.
18. Cohen JA, Baldassari LE, Atkins HL, Bowen JD, Bredeson C, Carpenter PA,et al. Autologous hematopoietic cell transplantation for treatment-refractory relapsing multiple sclerosis: position statement from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2019. doi: 10.1016/j.bbmt.2019.02.014.
19. Esmaeilizade Z, Mohammadi B, Omrani MD, Ghaderian SMH, Rajabibazl M, Fazeli Z. Preclinical studies and clinical trials with mesenchymal stem cell for demyelinating diseases: A systematic review. Curr Stem Cell Res Ther. 2021. doi: 10.2174/1574888X16666210208162318.
20. Chen Y, Shen J, Ke K, Gu X. Clinical potential and current progress of mesenchymal stem cells for Parkinson’s disease: a systematic review. Neurol Sci. 2020. doi: 10.1007/s10072-020-04240-9.
21. Madrazo I, Kopyov O, Ávila-Rodríguez MA, Ostrosky F, Carrasco H, Kopyov A, et al.Transplantation of Human Neural Progenitor Cells (NPC) into Putamina of Parkinsonian Patients: A Case Series Study, Safety and Efficacy Four Years after Surgery. Cell Transplant. 2018:963689718820271. doi: 10.1177/0963689718820271.
22. Takahasi J. Preparing for first human trial of induced pluripotent stem cell-derived cells for Parkinson’s disease: an interview with Jun Takahashi. Regen Med. 2019. doi: 10.2217/rme-2018-0158).
23. Stoddard-Bennett T, Reijo Pera R. Treatment of Parkinson’s Disease through Personalized Medicine and Induced Pluripotent Stem Cells. Cells. 2019;8(1). pii: E26. doi: 10.3390/cells8010026.
24. Parmar M, Grealish S, Henchcliffe C. The future of stem cell therapies for Parkinson’s disease. Nat Rev Neurosci. 2020 Jan 6. doi: 10.1038/s41583-019-0257-7.
25. Boika A, Aleinikava N, Chyzhyk V, Zafranskaya M, Nizheharodava D, Ponomarev V. Mesenchymal stem cells in Parkinson’s disease: Motor and nonmotor symptoms in the early post-transplant period. Surg Neurol Int. 2020;11:380.
26. Chen Y, Shen J, Ke K, Gu X. Clinical potential and current progress of mesenchymal stem cells for Parkinson’s disease: a systematic review. Neurol Sci. 2020;41(5):1051-1061. doi: 10.1007/s10072-020-04240-9. 27. Shin JY, Lee PH. Mesenchymal stem cells modulate misfolded α-synuclein in parkinsonian disorders: A multitarget disease-modifying strategy. Stem Cell Res. 2020;47:101908. doi: 10.1016/j.scr.2020.101908.
28. Zhang L, Dong ZF, Zhang JY. Immunomodulatory role of mesenchymal stem cells in Alzheimer’s disease. Life Sci. 2020;246:117405. doi: 10.1016/j.lfs.2020.117405.
29. Hour FQ, Moghadam AJ, Shakeri-Zadeh A, Bakhtiyari M, Shabani R, Mehdizadeh M. Magnetic targeted delivery of the SPIONs-labeled mesenchymal stem cells derived from human Wharton’s jelly in Alzheimer’s rat models. J Control Release. 2020:S0168-3659(20)30124-3. doi: 10.1016/j.jconrel.2020.02.035.
30. Zhang FQ, Jiang JL, Zhang JT, Niu H, Fu XQ, Zeng LL. Current status and future prospects of stem cell therapy in Alzheimer’s disease. Neural Regen Res. 2020;15(2):242-250. doi: 10.4103/1673-5374.265544.
31. Kim J, Lee Y, Lee S, Kim K, Song M, Lee J. Mesenchymal Stem Cell Therapy and Alzheimer’s Disease: Current Status and Future Perspectives. J Alzheimers Dis. 2020;77(1):1-14. doi: 10.3233/JAD-200219.
32. Zhang FQ, Jiang JL, Zhang JT, Niu H, Fu XQ, Zeng LL. Current status and future prospects of stem cell therapy in Alzheimer’s disease. Neural Regen Res. 2020;15(2):242-250. doi: 10.4103/1673-5374.265544.
33. Bagheri-Mohammadi S. Stem cell-based therapy as a promising approach in Alzheimer’s disease: current perspectives on novel treatment. Cell Tissue Bank. 2021. doi: 10.1007/s10561-020-09896-3.
34. Si Z, Wang X. Stem cells Therapies in Alzheimer’s disease: applications for disease modeling. J Pharmacol Exp Ther. 2021:JPET-MR-2020-000324. doi: 10.1124/jpet.120.000324.

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