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

Publisher: Humana Press Country of Publication: United States NLM ID: 8208561 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0291 (Electronic) Linking ISSN: 02732289 NLM ISO Abbreviation: Appl Biochem Biotechnol Subsets: MEDLINE

Original Publication: Clifton, N.J. : Humana Press, c1981-

Mesenchymal Stem Cell Transplantation* ; Nervous System Diseases*/therapy ; Neuroprotection*; Animals ; Child ; Humans ; Brain-Derived Neurotrophic Factor/metabolism ; Cerebral Palsy/therapy ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Nerve Growth Factors/metabolism ; Neurotrophin 3/metabolism ; Stroke/therapy

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.
Competing Interests: Declarations. Ethical Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mirza, F. J., & Zahid, S. (2018). The role of synapsins in neurological disorders. Neuroscience Bulletin, 34(2), 349–358. (PMID: 2928261210.1007/s12264-017-0201-7)
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. (PMID: 1726167810.1212/01.wnl.0000252807.38124.a3)
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. (PMID: 3132691610.1136/archdischild-2018-316519)
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. (PMID: 3633584010.1016/j.pediatrneurol.2022.09.005)
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. (PMID: 3552650110.1016/j.pedn.2022.04.014)
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. (PMID: 35952356980454710.1111/dmcn.15346)
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. (PMID: 10.14336/AD.2021.0219)
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. (PMID: 3446495210.1159/000518281)
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. (PMID: 31620481678920210.21037/sci.2019.08.11)
Cyranoski, D. (2019). Japan’s approval of stem-cell treatment for spinal-cord injury concerns scientists. Nature., 565(7737), 544–546. (PMID: 3069696310.1038/d41586-019-00178-x)
Hess, D. C., & Borlongan, C. (2008). Stem cells and neurological diseases. Cell Proliferation, 41, 94–114. (PMID: 1818195110.1111/j.1365-2184.2008.00486.x)
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. (PMID: 30028342606524310.4103/1673-5374.235085)
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. (PMID: 10.1186/s42269-019-0078-x)
Mukai, T., Tojo, A., & Nagamura-Inoue, T. (2018). Mesenchymal stromal cells as a potential therapeutic for neurological disorders. Regenerative Therapy, 9, 32–37. (PMID: 30525073622228310.1016/j.reth.2018.08.001)
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. (PMID: 10.1186/s13287-020-01839-9)
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. (PMID: 36058903944293810.1186/s12916-022-02482-2)
Morizane, A. (2023). Cell therapy for Parkinson’s disease with induced pluripotent stem cells. Inflammation and Regeneration, 43(1), 16–25. (PMID: 36843101996967810.1186/s41232-023-00269-3)
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. (PMID: 10.1002/path.2474)
Wagers, A. J. (2012). The stem cell niche in regenerative medicine. Cell Stem Cell, 10(4), 362–369. (PMID: 2248250210.1016/j.stem.2012.02.018)
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. (PMID: 2002263010.1016/j.biomaterials.2009.12.006)
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.
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. (PMID: 26765769488176510.1038/mt.2016.12)
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. (PMID: 34924958867590310.3389/fncel.2021.773375)
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. (PMID: 11160437676382110.1523/JNEUROSCI.21-02-00581.2001)
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. (PMID: 10.1186/s13287-021-02537-w)
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. (PMID: 35204719896166010.3390/biom12020218)
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. (PMID: 31218515675452310.1007/s12264-019-00405-5)
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. (PMID: 31515658692507310.1007/s12015-019-09917-z)
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. (PMID: 10.1155/2021/6676709)
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.
Law, S. M., & Zheng, J. J. (2022). Premise and peril of Wnt signaling activation through GSK-3β inhibition. Iscience, 25(4), 104159. (PMID: 35434563901064410.1016/j.isci.2022.104159)
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. (PMID: 25484855424006910.3389/fncel.2014.00393)
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. (PMID: 32586047735286010.3390/ijms21124471)
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. (PMID: 31298390)
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. (PMID: 33353235776594710.3390/ijms21249683)
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. (PMID: 10.1016/j.omtm.2017.06.005)
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. (PMID: 3444901310.1007/s12015-021-10219-6)
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. (PMID: 370582011010304810.1007/s12015-023-10539-9)
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. (PMID: 1278198610.1016/S0014-4886(03)00037-2)
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. (PMID: 10.1186/s13287-022-03024-6)
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. (PMID: 22980985344543210.1016/j.cell.2012.08.020)
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. (PMID: 10.1186/s13287-019-1276-z)
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. (PMID: 17225860176471810.1371/journal.pone.0000156)
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. (PMID: 10.1016/j.biopha.2022.113482)
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.
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. (PMID: 10.1177/0271678X20928147)
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. (PMID: 3157165810.4103/1673-5374.266058)
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. (PMID: 3379876510.1016/j.trsl.2021.03.017)
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. (PMID: 369827851005606210.3390/ijms24065712)
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. (PMID: 33871821809998910.1007/s12264-021-00667-y)
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. (PMID: 35303109896865710.1093/stcltm/szab022)
Patel, D. R., Neelakantan, M., Pandher, K., & Merrick, J. (2020). Cerebral palsy in children: A clinical overview. Translational Pediatrics, 9(Suppl 1), S125. (PMID: 32206590708224810.21037/tp.2020.01.01)
Paul, S., Nahar, A., Bhagawati, M., & Kunwar, A. J. (2022). A review on recent advances of cerebral palsy. Oxidative Medicine and Cellular Longevity, 2622310.
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. (PMID: 32606703729745410.2147/NDT.S235165)
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. (PMID: 3331842110.4103/1673-5374.300979)
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.
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. (PMID: 1909937410.1089/scd.2008.0253)
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. (PMID: 2129129710.1089/rej.2010.1130)
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. (PMID: 10.1111/cns.12441)
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. (PMID: 3038692310.1007/s00431-018-3279-7)
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. (PMID: 25422637423816410.4103/1673-5374.141785)
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. (PMID: 10.1523/ENEURO.0369-18.2018)
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. (PMID: 33559728826341610.1007/s00381-021-05068-0)
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.
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. (PMID: 10.3727/096368912X633806)
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. (PMID: 2464201610.1016/j.jcyt.2014.01.008)
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. (PMID: 29080265570251510.1002/sctm.17-0102)
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.
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.
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. (PMID: 1604904510.1093/brain/awh600)
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. (PMID: 10.1186/s13287-021-02513-4)
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. (PMID: 10.1093/braincomms/fcac131)
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. (PMID: 10.1186/s12883-022-02636-y)
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. (PMID: 35442487)
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. (PMID: 34085782838044010.1002/sctm.20-0470)
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. (PMID: 10.1186/s13287-022-03234-y)
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.
Numis, A. L., & Fox, C. K. (2014). Arterial ischemic stroke in children: Risk factors and etiologies. Current Neurology and Neuroscience Reports, 14, 1–9. (PMID: 10.1007/s11910-013-0422-8)
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.
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. (PMID: 35203560896238710.3390/biomedicines10020353)
Guzman, R., Janowski, M., & Walczak, P. (2018). Intra-arterial delivery of cell therapies for stroke. Stroke., 49(5), 1075–1082. (PMID: 29669876602763810.1161/STROKEAHA.117.018288)
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. (PMID: 3347292510.1212/WNL.0000000000011440)
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. (PMID: 3276150510.1007/s00415-020-10138-5)
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. (PMID: 33737862796093010.3389/fnins.2021.641970)
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. (PMID: 36836645996290110.3390/life13020288)
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. (PMID: 10.1021/acsbiomaterials.2c00228)
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. (PMID: 26946534495037910.1177/1535370216636722)
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. (PMID: 3152966310.1002/stem.3080)
Shenoy, S. (2013). Hematopoietic stem-cell transplantation for sickle cell disease: Current evidence and opinions. Therapeutic Advances in Hematology, 4(5), 335–344. (PMID: 24082994376634710.1177/2040620713483063)
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. (PMID: 3408618510.1007/s11764-021-01063-1)
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. (PMID: 30639825651132710.1016/j.bbmt.2019.01.008)
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.
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. (PMID: 35356638892919910.14740/jh949)
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. (PMID: 10.1038/s41572-019-0138-4)
Jure, R. (2019). Autism pathogenesis: The superior colliculus. Frontiers in Neuroscience, 12, 1029–1041. (PMID: 30686990633474610.3389/fnins.2018.01029)
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.
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. (PMID: 2625713710.1002/aur.1530)
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. (PMID: 2839232310.1016/j.bbr.2017.03.047)
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. (PMID: 3177341010.1007/s12035-019-01811-6)
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. (PMID: 10.1186/s13229-020-00366-x)
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.
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. (PMID: 10.1186/1479-5876-11-196)
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. (PMID: 29405603586692710.1002/sctm.17-0042)
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. (PMID: 30620122634489910.1002/sctm.18-0251)
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.
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. (PMID: 32531111751977310.1002/sctm.19-0434)
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. (PMID: 3315070310.1111/appy.12445)

Keywords: Mesenchymal stem cells; Neuroprotection; Pediatric neurological disease

0 (Brain-Derived Neurotrophic Factor)
0 (Nerve Growth Factors)
0 (Neurotrophin 3)

Date Created: 20240123 Date Completed: 20241128 Latest Revision: 20241210

20250114

10.1007/s12010-023-04752-y

38261236