Skip to main content
Log in

Mesenchymal Stem Cell-Induced Neuroprotection in Pediatric Neurological Diseases: Recent Update of Underlying Mechanisms and Clinical Utility

  • Review Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Pediatric neurological diseases refer to a group of disorders that affect the nervous system in children. These conditions can have a significant impact on a child’s development, cognitive function, motor skills, and overall quality of life. Stem cell therapy is a new and innovative approach to treat various neurological conditions by repairing damaged neurons and replacing those that have been lost. Mesenchymal stem cells (MSCs) have gained significant recognition in this regard due to their ability to differentiate into different cell types. MSCs are multipotent self-replicating stem cells known to render promising results in the treatment of stroke and spinal cord injury in adults. When delivered to the foci of damage in the central nervous system, stem cells begin to differentiate into neural cells under the stimulation of paracrine factors and secrete various neurotrophic factors (NTFs) like nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) that expedite the repair process in injured neurons. In the present review, we will focus on the therapeutic benefits of the MSC-based therapies in salient pediatric neurological disorders including cerebral palsy, stroke, and autism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

Declaration of data availability does not correspond to this type of publication.

References

  1. Mirza, F. J., & Zahid, S. (2018). The role of synapsins in neurological disorders. Neuroscience Bulletin, 34(2), 349–358.

    Article  CAS  PubMed  Google Scholar 

  2. Hirtz, D., Thurman, D. J., Gwinn-Hardy, K., Mohamed, M., Chaudhuri, A., & Zalutsky, R. (2007). How common are the “common” neurologic disorders? Neurology., 68(5), 326–337.

    Article  CAS  PubMed  Google Scholar 

  3. Raper, J., Currigan, V., Fothergill, S., Stone, J., & Forsyth, R. J. (2019). Long-term outcomes of functional neurological disorder in children. Archives of Disease in Childhood, 104(12), 1155–1160.

    Article  PubMed  Google Scholar 

  4. Chand, P., Sultan, T., Kulsoom, S., Jan, F., Ibrahim, S., Mukhtiar, K., et al. (2023). Spectrum of common pediatric neurological disorders: A cross-sectional study from three tertiary care centres across Pakistan. Pediatric Neurology, 138, 33–37.

    Article  PubMed  Google Scholar 

  5. Kilmer, M., & Boykin, A. (2022). Analysis of the 2000 to 2018 autism and developmental disabilities monitoring network surveillance reports: Implications for primary care clinicians. Journal of Pediatric Nursing, 65, 55–68.

    Article  PubMed  Google Scholar 

  6. McIntyre, S., Goldsmith, S., Webb, A., Ehlinger, V., Hollung, S. J., McConnell, K., et al. (2022). Global prevalence of cerebral palsy: A systematic analysis. Developmental Medicine and Child Neurology, 64(12), 1494–1506.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hollist, M., Au, K., Morgan, L., Shetty, P. A., Rane, R., Hollist, A., et al. (2021). Pediatric stroke: Overview and recent updates. Aging & Disease, 12(4), 1043–1048.

    Article  Google Scholar 

  8. Oleske, D. M., Cheng, X., Jeong, A., & Arndt, T. J. (2021). Pediatric acute ischemic stroke by age-group: A systematic review and meta-analysis of published studies and hospitalization records. Neuroepidemiology., 55(5), 331–341.

    Article  PubMed  Google Scholar 

  9. Saeedi, P., Halabian, R., & Fooladi, A. A. I. (2019). A revealing review of mesenchymal stem cells therapy, clinical perspectives and modification strategies. Stem Cell Investigation, 6, 34–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cyranoski, D. (2019). Japan’s approval of stem-cell treatment for spinal-cord injury concerns scientists. Nature., 565(7737), 544–546.

    Article  CAS  PubMed  Google Scholar 

  11. Hess, D. C., & Borlongan, C. (2008). Stem cells and neurological diseases. Cell Proliferation, 41, 94–114.

    Article  PubMed  Google Scholar 

  12. Song, C.-G., Zhang, Y.-Z., Wu, H.-N., Cao, X.-L., Guo, C.-J., Li, Y.-Q., et al. (2018). Stem cells: A promising candidate to treat neurological disorders. Neural Regeneration Research, 13(7), 1294–1299.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fouad, G. I. (2019). Stem cells as a promising therapeutic approach for Alzheimer’s disease: A review. Bulletin of the National Research Centre, 43(1), 1–20.

    Article  Google Scholar 

  14. Mukai, T., Tojo, A., & Nagamura-Inoue, T. (2018). Mesenchymal stromal cells as a potential therapeutic for neurological disorders. Regenerative Therapy, 9, 32–37.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Li, Z., Dong, X., Tian, M., Liu, C., Wang, K., Li, L., et al. (2020). Stem cell-based therapies for ischemic stroke: A systematic review and meta-analysis of clinical trials. Stem Cell Research & Therapy, 11, 1–13.

    Article  Google Scholar 

  16. Shang, Z., Wang, M., Zhang, B., Wang, X., & Wanyan, P. (2022). Clinical translation of stem cell therapy for spinal cord injury still premature: Results from a single-arm meta-analysis based on 62 clinical trials. BMC Medicine, 20(1), 284–291.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Morizane, A. (2023). Cell therapy for Parkinson’s disease with induced pluripotent stem cells. Inflammation and Regeneration, 43(1), 16–25.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Walker, M., Patel, K., & Stappenbeck, T. (2009). The stem cell niche. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland., 217(2), 169–180.

    Article  CAS  Google Scholar 

  19. Wagers, A. J. (2012). The stem cell niche in regenerative medicine. Cell Stem Cell, 10(4), 362–369.

    Article  CAS  PubMed  Google Scholar 

  20. Tang, J., Peng, R., & Ding, J. (2010). The regulation of stem cell differentiation by cell-cell contact on micropatterned material surfaces. Biomaterials., 31(9), 2470–2476.

    Article  CAS  PubMed  Google Scholar 

  21. Hosseini, K., Lekholm, E., Ahemaiti, A., & Fredriksson, R. (2020). Differentiation of human embryonic stem cells into neuron, cholinergic, and glial cells. Stem Cells International, 8827874.

  22. Pollock, K., Dahlenburg, H., Nelson, H., Fink, K. D., Cary, W., Hendrix, K., et al. (2016). Human mesenchymal stem cells genetically engineered to overexpress brain-derived neurotrophic factor improve outcomes in Huntington’s disease mouse models. Molecular Therapy, 24(5), 965–977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang, L., Gu, S., Gan, J., Tian, Y., Zhang, F., Zhao, H., et al. (2021). Neural stem cells overexpressing nerve growth factor improve functional recovery in rats following spinal cord injury via modulating microenvironment and enhancing endogenous neurogenesis. Frontiers in Cellular Neuroscience, 15, 773375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Erickson, J. T., Brosenitsch, T. A., & Katz, D. M. (2001). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor are required simultaneously for survival of dopaminergic primary sensory neurons in vivo. The Journal of Neuroscience, 21(2), 581–589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Huang, F., Gao, T., Wang, W., Wang, L., Xie, Y., Tai, C., et al. (2021). Engineered basic fibroblast growth factor-overexpressing human umbilical cord-derived mesenchymal stem cells improve the proliferation and neuronal differentiation of endogenous neural stem cells and functional recovery of spinal cord injury by activating the PI3K-Akt-GSK-3β signaling pathway. Stem Cell Research & Therapy, 12(1), 1–18.

    Article  CAS  Google Scholar 

  26. Koutsoumparis, A. E., Patsiarika, A., Tsingotjidou, A., Pappas, I., & Tsiftsoglou, A. S. (2022). Neural differentiation of human dental mesenchymal stem cells induced by ATRA and UDP-4: A comparative study. Biomolecules, 12(2), 218–227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tian, L., Zhu, W., Liu, Y., Gong, Y., Lv, A., Wang, Z., et al. (2019). Neural stem cells transfected with leukemia inhibitory factor promote neuroprotection in a rat model of cerebral ischemia. Neuroscience Bulletin, 35, 901–908.

    Article  PubMed  PubMed Central  Google Scholar 

  28. George, S., Hamblin, M. R., & Abrahamse, H. (2019). Differentiation of mesenchymal stem cells to neuroglia: In the context of cell signalling. Stem Cell Reviews and Reports, 15, 814–826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang, J., Yang, B., Luo, L., Li, L., Yang, X., Zhang, J., et al. (2021). Effect of NTN and Lmx1α on the notch signaling pathway during the differentiation of human bone marrow mesenchymal stem cells into dopaminergic neuron-like cells. Parkinson's Disease, 2021, 1–11.

    Article  Google Scholar 

  30. Maeda S, Miyagawa S, Kawamura T, Shibuya T, Watanabe K, Nakagawa T, et al. (2021). Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model. Scientific Reports, 11(1):1-9.

  31. Law, S. M., & Zheng, J. J. (2022). Premise and peril of Wnt signaling activation through GSK-3β inhibition. Iscience, 25(4), 104159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Stipursky, J., Francis, D., Dezonne, R. S., Bérgamo de Araújo, A. P., Souza, L., Moraes, C. A., et al. (2014). TGF-β 1 promotes cerebral cortex radial glia-astrocyte differentiation in vivo. Frontiers in Cellular Neuroscience, 8, 393–402.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Albert-Gascó, H., Ros-Bernal, F., Castillo-Gómez, E., & Olucha-Bordonau, F. E. (2020). MAP/ERK signaling in developing cognitive and emotional function and its effect on pathological and neurodegenerative processes. International Journal of Molecular Sciences, 21(12), 4471–4478.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wang, Q., Lu, L., & Zhou, H. (2019). Relationship between the MAPK/ERK pathway and neurocyte apoptosis after cerebral infarction in rats. European Review for Medical and Pharmacological Sciences, 23(12), 5374–5381.

    PubMed  Google Scholar 

  35. Salari, V., Mengoni, F., Del Gallo, F., Bertini, G., & Fabene, P. F. (2020). The anti-inflammatory properties of mesenchymal stem cells in epilepsy: Possible treatments and future perspectives. International Journal of Molecular Sciences, 21(24), 9683–9690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nakajima, M., Nito, C., Sowa, K., Suda, S., Nishiyama, Y., Nakamura-Takahashi, A., et al. (2017). Mesenchymal stem cells overexpressing interleukin-10 promote neuroprotection in experimental acute ischemic stroke. Molecular Therapy-Methods & Clinical Development, 6, 102–111.

    Article  CAS  Google Scholar 

  37. Han, T., Song, P., Wu, Z., Xiang, X., Liu, Y., Wang, Y., et al. (2022). MSC secreted extracellular vesicles carrying TGF-beta upregulate Smad 6 expression and promote the regrowth of neurons in spinal cord injured rats. Stem Cell Reviews and Reports, 18(3), 1078–1096.

    Article  CAS  PubMed  Google Scholar 

  38. Yang, G., Fan, X., Liu, Y., Jie, P., Mazhar, M., Liu, Y., et al. (2023). Immunomodulatory mechanisms and therapeutic potential of mesenchymal stem cells. Stem Cell Reviews and Reports, 19, 1214–1231.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Lu, P., Jones, L., Snyder, E., & Tuszynski, M. (2003). Neural stem cells constitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Experimental Neurology, 181(2), 115–129.

    Article  CAS  PubMed  Google Scholar 

  40. Bahlakeh, G., Rahbarghazi, R., Abedelahi, A., Sadigh-Eteghad, S., & Karimipour, M. (2022). Neurotrophic factor-secreting cells restored endogenous hippocampal neurogenesis through the Wnt/β-catenin signaling pathway in AD model mice. Stem Cell Research & Therapy, 13(1), 1–14.

    Article  Google Scholar 

  41. Lu, P., Wang, Y., Graham, L., McHale, K., Gao, M., Wu, D., et al. (2012). Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell., 150(6), 1264–1273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bian, X., Ma, K., Zhang, C., & Fu, X. (2019). Therapeutic angiogenesis using stem cell-derived extracellular vesicles: an emerging approach for treatment of ischemic diseases. Stem Cell Research & Therapy, 10(1), 1–18.

    Article  CAS  Google Scholar 

  43. Lee, H. J., Kim, K. S., Park, I. H., & Kim, S. U. (2007). Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model. PLoS One, 2(1), e156.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Zhang, L., Liu, Q., Hu, H., Zhao, L., & Zhu, K. (2022). Progress in mesenchymal stem cell mitochondria transfer for the repair of tissue injury and treatment of disease. Biomedicine & Pharmacotherapy, 153, 113482.

    Article  CAS  Google Scholar 

  45. Han, D., Zheng, X., Wang, X., Jin, T., Cui, L., & Chen, Z. (2020). Mesenchymal stem/stromal cell-mediated mitochondrial transfer and the therapeutic potential in treatment of neurological diseases. Stem Cells International, 8838046.

  46. Tseng, N., Lambie, S. C., Huynh, C. Q., Sanford, B., Patel, M., Herson, P. S., et al. (2021). Mitochondrial transfer from mesenchymal stem cells improves neuronal metabolism after oxidant injury in vitro: The role of Miro1. Journal of Cerebral Blood Flow & Metabolism, 41(4), 761–770.

    Article  CAS  Google Scholar 

  47. Yang, Y., Ye, G., Zhang, Y.-L., He, H.-W., Yu, B.-Q., Hong, Y.-M., et al. (2020). Transfer of mitochondria from mesenchymal stem cells derived from induced pluripotent stem cells attenuates hypoxia-ischemia-induced mitochondrial dysfunction in PC12 cells. Neural Regeneration Research, 15(3), 464–479.

    Article  CAS  PubMed  Google Scholar 

  48. Zhao, J., Qu, D., Xi, Z., Huan, Y., Zhang, K., Yu, C., et al. (2021). Mitochondria transplantation protects traumatic brain injury via promoting neuronal survival and astrocytic BDNF. Translational Research, 235, 102–114.

    Article  CAS  PubMed  Google Scholar 

  49. Seo, Y., Han, S., Song, B.-W., Chang, J. W., Na, Y. C., & Chang, W. S. (2023). Endogenous neural stem cell activation after low-intensity focused ultrasound-induced blood–Brain barrier modulation. International Journal of Molecular Sciences, 24(6), 5712–5728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Yuan, T.-F., Dong, Y., Zhang, L., Qi, J., Yao, C., Wang, Y., et al. (2021). Neuromodulation-based stem cell therapy in brain repair: Recent advances and future perspectives. Neuroscience Bulletin, 37, 735–745.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Alshoubaki, Y. K., Nayer, B., Das, S., & Martino, M. M. (2022). Modulation of the activity of stem and progenitor cells by immune cells. Stem Cells Translational Medicine, 11(3), 248–258.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Patel, D. R., Neelakantan, M., Pandher, K., & Merrick, J. (2020). Cerebral palsy in children: A clinical overview. Translational Pediatrics, 9(Suppl 1), S125.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Paul, S., Nahar, A., Bhagawati, M., & Kunwar, A. J. (2022). A review on recent advances of cerebral palsy. Oxidative Medicine and Cellular Longevity, 2622310.

  54. Sadowska, M., Sarecka-Hujar, B., & Kopyta, I. (2020). Cerebral palsy: Current opinions on definition, epidemiology, risk factors, classification and treatment options. Neuropsychiatric Disease and Treatment, 16, 1505–1525.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lv, Z.-Y., Li, Y., & Liu, J. (2021). Progress in clinical trials of stem cell therapy for cerebral palsy. Neural Regeneration Research, 16(7), 1377–1392.

    Article  PubMed  Google Scholar 

  56. Pan, K., Deng, L., Chen, P., Peng, Q., Pan, J., Wu, Y., et al. (2019). Safety and feasibility of repeated intrathecal allogeneic bone marrow-derived mesenchymal stromal cells in patients with neurological diseases. Stem Cells International, 8421281.

  57. Fischer, U. M., Harting, M. T., Jimenez, F., Monzon-Posadas, W. O., Xue, H., Savitz, S. I., et al. (2009). Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells and Development, 18(5), 683–692.

    Article  CAS  PubMed  Google Scholar 

  58. Danielyan, L., Schäfer, R., von Ameln-Mayerhofer, A., Bernhard, F., Verleysdonk, S., Buadze, M., et al. (2011). Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease. Rejuvenation Research, 14(1), 3–16.

    Article  CAS  PubMed  Google Scholar 

  59. Ji, G., Liu, M., Zhao, X. F., Liu, X. Y., Guo, Q. L., Guan, Z. F., et al. (2015). NF-κB signaling is involved in the effects of intranasally engrafted human neural stem cells on neurofunctional improvements in neonatal rat hypoxic–Ischemic encephalopathy. CNS Neuroscience & Therapeutics, 21(12), 926–935.

    Article  CAS  Google Scholar 

  60. Keller, T., Körber, F., Oberthuer, A., Schafmeyer, L., Mehler, K., Kuhr, K., et al. (2019). Intranasal breast milk for premature infants with severe intraventricular hemorrhage—An observation. European Journal of Pediatrics, 178(2), 199–206.

    Article  CAS  PubMed  Google Scholar 

  61. Tan, J., Zheng, X., Zhang, S., Yang, Y., Wang, X., Yu, X., et al. (2014). Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells. Neural Regeneration Research, 9(19), 1763–1782.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Rumajogee, P., Altamentova, S., Li, L., Li, J., Wang, J., Kuurstra, A., et al. (2018). Exogenous neural precursor cell transplantation results in structural and functional recovery in a hypoxic-ischemic hemiplegic mouse model. Eneuro, 5(5), 369–380.

    Article  Google Scholar 

  63. Chang, Y., Lin, S., Li, Y., Liu, S., Ma, T., & Wei, W. (2021). Umbilical cord blood CD34+ cells administration improved neurobehavioral status and alleviated brain injury in a mouse model of cerebral palsy. Child's Nervous System, 37, 2197–2205.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Purandare, C., Shitole, D., Belle, V., Kedari, A., Bora, N., & Joshi, M. (2012). Therapeutic potential of autologous stem cell transplantation for cerebral palsy. Case Reports in Transplantation, 825289.

  65. Luan, Z., Liu, W., Qu, S., Du, K., He, S., Wang, Z., et al. (2012). Effects of neural progenitor cell transplantation in children with severe cerebral palsy. Cell Transplantation, 21(1_suppl), 91–98.

    Article  Google Scholar 

  66. Mancías-Guerra, C., Marroquín-Escamilla, A. R., González-Llano, O., Villarreal-Martínez, L., Jaime-Pérez, J. C., García-Rodríguez, F., et al. (2014). Safety and tolerability of intrathecal delivery of autologous bone marrow nucleated cells in children with cerebral palsy: An open-label phase I trial. Cytotherapy., 16(6), 810–820.

    Article  PubMed  Google Scholar 

  67. Sun, J. M., Song, A. W., Case, L. E., Mikati, M. A., Gustafson, K. E., Simmons, R., et al. (2017). Effect of autologous cord blood infusion on motor function and brain connectivity in young children with cerebral palsy: A randomized, placebo-controlled trial. Stem Cells Translational Medicine, 6(12), 2071–2078.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Gu J, Huang L, Zhang C, Wang Y, Zhang R, Tu Z, et al. (2020). Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: A randomized, controlled trial. Stem Cell Research & Therapy, 11(1):1-12.

  69. Min K, Suh MR, Cho KH, Park W, Kang MS, Jang SJ, et al. (2020). Potentiation of cord blood cell therapy with erythropoietin for children with CP: A 2× 2 factorial randomized placebo-controlled trial. Stem Cell Research & Therapy, 11(1), 1-12.

  70. Thomas, B., Eyssen, M., Peeters, R., Molenaers, G., Van Hecke, P., De Cock, P., et al. (2005). Quantitative diffusion tensor imaging in cerebral palsy due to periventricular white matter injury. Brain., 128(11), 2562–2577.

    Article  PubMed  Google Scholar 

  71. Amanat, M., Majmaa, A., Zarrabi, M., Nouri, M., Akbari, M. G., Moaiedi, A. R., et al. (2021). Clinical and imaging outcomes after intrathecal injection of umbilical cord tissue mesenchymal stem cells in cerebral palsy: A randomized double-blind sham-controlled clinical trial. Stem Cell Research & Therapy, 12(1), 1–15.

    Article  Google Scholar 

  72. Cox, C. S., Juranek, J., Kosmach, S., Pedroza, C., Thakur, N., Dempsey, A., et al. (2022). Autologous cellular therapy for cerebral palsy: A randomized, crossover trial. Brain Communications, 4(3), 131–143.

    Article  Google Scholar 

  73. Zarrabi, M., Akbari, M. G., Amanat, M., Majmaa, A., Moaiedi, A. R., Montazerlotfelahi, H., et al. (2022). The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: A randomized double-blind sham-controlled clinical trial. BMC Neurology, 22(1), 1–13.

    Article  Google Scholar 

  74. Maric, D., Radomir, M., Milankov, Z., Stanojevic, I., Vojvodic, D., Velikic, G., et al. (2022). Encouraging effect of autologous bone marrow aspirate concentrate in rehabilitation of children with cerebral palsy. European Review for Medical and Pharmacological Sciences, 26(7), 2330–2342.

    CAS  PubMed  Google Scholar 

  75. Sun, J. M., Case, L. E., Mikati, M. A., Jasien, J. M., McLaughlin, C., Waters-Pick, B., et al. (2021). Sibling umbilical cord blood infusion is safe in young children with cerebral palsy. Stem Cells Translational Medicine, 10(9), 1258–1265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lv, Z., Li, Y., Wang, Y., Cong, F., Li, X., Cui, W., et al. (2023). Safety and efficacy outcomes after intranasal administration of neural stem cells in cerebral palsy: A randomized phase 1/2 controlled trial. Stem Cell Research & Therapy, 14(1), 1–14.

    Article  Google Scholar 

  77. Gautam, J., Alaref, A., Hassan, A., Kandel, R. S., Mishra, R., & Jahan, N. (2020). Safety and efficacy of stem cell therapy in patients with ischemic stroke. Cureus., 12(8), 917–930.

    Google Scholar 

  78. Numis, A. L., & Fox, C. K. (2014). Arterial ischemic stroke in children: Risk factors and etiologies. Current Neurology and Neuroscience Reports, 14, 1–9.

    Article  CAS  Google Scholar 

  79. Sanchez-Diaz, M., Quiñones-Vico, M. I., Sanabria de la Torre, R., Montero-Vílchez, T., Sierra-Sánchez, A., Molina-Leyva, A., et al. (2021). Biodistribution of mesenchymal stromal cells after administration in animal models and humans: A systematic review. Journal of. Clinical Medicine, 10(13), 2925–2940.

    Google Scholar 

  80. Gubskiy, I. L., Namestnikova, D. D., Revkova, V. A., Cherkashova, E. A., Sukhinich, K. K., Beregov, M. M., et al. (2022). The impact of cerebral perfusion on mesenchymal stem cells distribution after intra-arterial transplantation: A quantitative MR study. Biomedicines, 10(2), 353–369.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Guzman, R., Janowski, M., & Walczak, P. (2018). Intra-arterial delivery of cell therapies for stroke. Stroke., 49(5), 1075–1082.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Chung, J.-W., Chang, W. H., Bang, O. Y., Moon, G. J., Kim, S. J., Kim, S.-K., et al. (2021). Efficacy and safety of intravenous mesenchymal stem cells for ischemic stroke. Neurology., 96(7), e1012–e1e23.

    Article  CAS  PubMed  Google Scholar 

  83. Li, J., Zhang, Q., Wang, W., Lin, F., Wang, S., & Zhao, J. (2021). Mesenchymal stem cell therapy for ischemic stroke: A look into treatment mechanism and therapeutic potential. Journal of Neurology, 268, 4095–4107.

    Article  PubMed  Google Scholar 

  84. Namestnikova, D. D., Gubskiy, I. L., Revkova, V. A., Sukhinich, K. K., Melnikov, P. A., Gabashvili, A. N., et al. (2021). Intra-arterial stem cell transplantation in experimental stroke in rats: Real-time MR visualization of transplanted cells starting with their first pass through the brain with regard to the therapeutic action. Frontiers in Neuroscience, 15, 641970.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Cherkashova, E. A., Namestnikova, D. D., Gubskiy, I. L., Revkova, V. A., Sukhinich, K. K., Melnikov, P. A., et al. (2023). Dynamic MRI of the mesenchymal stem cells distribution during intravenous transplantation in a rat model of ischemic stroke. Life, 13(2), 288–298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Xu, R., Duan, C., Meng, Z., Zhao, J., He, Q., Zhang, Q., et al. (2022). Lipid microcapsules promoted neural stem cell survival in the infarcted area of mice with ischemic stroke by inducing autophagy. ACS Biomaterials Science & Engineering, 8(10), 4462–4473.

    Article  CAS  Google Scholar 

  87. Rivera, C. P., Veneziani, A., Ware, R. E., & Platt, M. O. (2016). Sickle cell anemia and pediatric strokes: computational fluid dynamics analysis in the middle cerebral artery. Experimental Biology and Medicine, 241(7), 755–765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Vahidy, F. S., Haque, M. E., Rahbar, M. H., Zhu, H., Rowan, P., Aisiku, I. P., et al. (2019). Intravenous bone marrow mononuclear cells for acute ischemic stroke: Safety, feasibility, and effect size from a phase I clinical trial. Stem Cells, 37(11), 1481–1491.

    Article  CAS  PubMed  Google Scholar 

  89. Shenoy, S. (2013). Hematopoietic stem-cell transplantation for sickle cell disease: Current evidence and opinions. Therapeutic Advances in Hematology, 4(5), 335–344.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Wu, N. L., Krull, K. R., Cushing-Haugen, K. L., Ullrich, N. J., Kadan-Lottick, N. S., Lee, S. J., et al. (2022). Long-term neurocognitive and quality of life outcomes in survivors of pediatric hematopoietic cell transplant. Journal of Cancer Survivorship, 16(3), 696–704.

    Article  PubMed  Google Scholar 

  91. King, A. A., McKinstry, R. C., Wu, J., Eapen, M., Abel, R., Varughese, T., et al. (2019). Functional and radiologic assessment of the brain after reduced-intensity unrelated donor transplantation for severe sickle cell disease: Blood and marrow transplant clinical trials network study 0601. Biology of Blood and Marrow Transplantation, 25(5), e174–e1e8.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Carpenter, J. L., Nickel, R. S., Webb, J., Khademian, Z., Speller-Brown, B., Majumdar, S., et al. (2021). Low rates of cerebral infarction after hematopoietic stem cell transplantation in patients with sickle cell disease at high risk for stroke. Transplantation and Cellular. Therapy., 27(12), 1018 e1-. e9.

    Google Scholar 

  93. Al-Jefri, A., Siddiqui, K., Al-Oraibi, A., Al-Seraihy, A., Al Ahmari, A., Ghemlas, I., et al. (2022). Hematopoietic stem cell transplantation stabilizes cerebral vasculopathy in high-risk pediatric sickle cell disease patients: Evidence from a referral transplant center. Journal of Hematology, 11(1), 8–24.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Lord, C., Brugha, T. S., Charman, T., Cusack, J., Dumas, G., Frazier, T., et al. (2020). Autism spectrum disorder. Nature Reviews. Disease Primers, 6(1), 1–23.

    Article  Google Scholar 

  95. Jure, R. (2019). Autism pathogenesis: The superior colliculus. Frontiers in Neuroscience, 12, 1029–1041.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Medavarapu, S., Marella, L. L., Sangem, A., & Kairam, R. (2019). Where is the evidence? A narrative literature review of the treatment modalities for autism spectrum disorders. Cureus, 11(1), 390–399.

    Google Scholar 

  97. Segal-Gavish, H., Karvat, G., Barak, N., Barzilay, R., Ganz, J., Edry, L., et al. (2016). Mesenchymal stem cell transplantation promotes neurogenesis and ameliorates autism related behaviors in BTBR mice. Autism Research, 9(1), 17–32.

    Article  PubMed  Google Scholar 

  98. Perets, N., Segal-Gavish, H., Gothelf, Y., Barzilay, R., Barhum, Y., Abramov, N., et al. (2017). Long term beneficial effect of neurotrophic factors-secreting mesenchymal stem cells transplantation in the BTBR mouse model of autism. Behavioural Brain Research, 331, 254–260.

    Article  CAS  PubMed  Google Scholar 

  99. Grasselli, C., Carbone, A., Panelli, P., Giambra, V., Bossi, M., Mazzoccoli, G., et al. (2020). Neural stem cells from Shank3-ko mouse model autism spectrum disorders. Molecular Neurobiology, 57, 1502–1515.

    Article  CAS  PubMed  Google Scholar 

  100. Perets, N., Oron, O., Herman, S., Elliott, E., & Offen, D. (2020). Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B. Molecular Autism, 11(1), 1–13.

    Article  Google Scholar 

  101. Liu, M., Lü, Y.-t, Huan, Y., Ge, R.-c, Zhang, J., SGC-Q, J., et al. (2011). Safety and efficacy of cord blood mononuclear cells and umbilical cord mesenchymal stem cells therapy for childhood autism. Chinese Journal of Tissue Engineering. Research, 15(23), 4359–4373.

    Google Scholar 

  102. Lv, Y.-T., Zhang, Y., Liu, M., Ashwood, P., Cho, S. C., Huan, Y., et al. (2013). Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. Journal of Translational Medicine, 11(1), 1–10.

    Article  Google Scholar 

  103. Chez, M., Lepage, C., Parise, C., Dang-Chu, A., Hankins, A., & Carroll, M. (2018). Safety and observations from a placebo-controlled, crossover study to assess use of autologous umbilical cord blood stem cells to improve symptoms in children with autism. Stem Cells Translational Medicine, 7(4), 333–341.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Carpenter, K. L., Major, S., Tallman, C., Chen, L. W., Franz, L., Sun, J., et al. (2019). White matter tract changes associated with clinical improvement in an open-label trial assessing autologous umbilical cord blood for treatment of young children with autism. Stem Cells Translational Medicine, 8(2), 138–147.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Dawson, G., Sun, J. M., Baker, J., Carpenter, K., Compton, S., Deaver, M., et al. (2020). A phase II randomized clinical trial of the safety and efficacy of intravenous umbilical cord blood infusion for treatment of children with autism spectrum disorder. The Journal of Pediatrics, 222(164-73), e5.

    Google Scholar 

  106. Sun, J. M., Dawson, G., Franz, L., Howard, J., McLaughlin, C., Kistler, B., et al. (2020). Infusion of human umbilical cord tissue mesenchymal stromal cells in children with autism spectrum disorder. Stem Cells Translational Medicine, 9(10), 1137–1146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sharifzadeh, N., Ghasemi, A., Tavakol Afshari, J., Moharari, F., Soltanifar, A., Talaei, A., et al. (2021). Intrathecal autologous bone marrow stem cell therapy in children with autism: A randomized controlled trial. Asia-Pacific Psychiatry, 13(2), e12445.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Manuscript writing: WC and QR contributed equally. WL corrected the final version of the manuscript.

Corresponding author

Correspondence to Wenchun Liu.

Ethics declarations

Ethical Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, W., Ren, Q., Zhou, J. et al. Mesenchymal Stem Cell-Induced Neuroprotection in Pediatric Neurological Diseases: Recent Update of Underlying Mechanisms and Clinical Utility. Appl Biochem Biotechnol (2024). https://doi.org/10.1007/s12010-023-04752-y

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12010-023-04752-y

Keywords

Navigation