Skip to main content

Advertisement

SpringerLink
Log in

Neural Stem Cells Therapy for Ischemic Stroke: Progress and Challenges

  • Review Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

Ischemic stroke, with its high morbidity and mortality, is the most common cerebrovascular accident and results in severe neurological deficits. Despite advances in medical and surgical intervention, post-stroke therapies remain scarce, which seriously affects the quality of life of patients. Over the past decades, stem cell transplantation has been recognized as very promising therapy for neurological diseases. Neural stem cell (NSC) transplantation is the optimal choice for ischemic stroke as NSCs inherently reside in the brain and can potentially differentiate into a variety of cell types within the central nervous system. Recent research has demonstrated that NSC transplantation can facilitate neural recovery after ischemic stroke, but the mechanisms still remain unclear, and basic/clinical studies of NSC transplantation for ischemic stroke have not yet been thoroughly elucidated. We thus, in this review, provide a futher understanding of the therapeutic role of NSCs for ischemic stroke, and evaluate their prospects for future application in clinical patients of ischemic stroke.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Powers WJ. Acute ischemic stroke. N Engl J Med. 2020;383(3):252–60.

    Article  PubMed  Google Scholar 

  2. Campbell BCV, Khatri P. Stroke. Lancet. 2020;396(10244):129–42.

    Article  PubMed  Google Scholar 

  3. Zhu J, Wu X, Zhang HL. Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical transplantation. Curr Drug Targets. 2005;6(1):97–110.

    Article  CAS  PubMed  Google Scholar 

  4. Zhu J, Zhou L, Wu X. Tracking neural stem cells in patients with brain trauma. N Engl J Med. 2006;355(22):2376–8.

    Article  CAS  PubMed  Google Scholar 

  5. Tang HL, Sun HP, Wu X, et al. Detection of neural stem cells function in rats with traumatic brain injury by manganese-enhanced magnetic resonance imaging. Chin Med J (Engl). 2011;124(12):1848–53.

    Google Scholar 

  6. Tang H, Sha H, Sun H, et al. Tracking induced pluripotent stem cells-derived neural stem cells in the central nervous system of rats and monkeys. Cell Reprogram. 2013;15(5):435–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Jiang L, Li R, Tang H, et al. MRI tracking of iPS cells-induced neural stem cells in traumatic brain injury rats. Cell Transplant. 2019;28(6):747–55.

    Article  PubMed  Google Scholar 

  8. Gonçalves JT, Schafer ST, Gage FH. Adult neurogenesis in the hippocampus: from stem cells to behavior. Cell. 2016;167(4):897–914.

    Article  PubMed  CAS  Google Scholar 

  9. Yang SH, Liu R. Four decades of ischemic penumbra and its implication for ischemic stroke. Transl Stroke Res. 2021. https://doi.org/10.1007/s12975-021-00916-2.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Richards LG, Cramer SC. Advances in stroke: therapies targeting stroke recovery. Stroke. 2021;52(1):348–50.

    Article  CAS  PubMed  Google Scholar 

  11. Park YJ, Niizuma K, Mokin M, et al. Cell-based therapy for stroke: musing with muse cells. Stroke. 2020;51(9):2854–62.

    Article  PubMed  Google Scholar 

  12. Wang F, Tang H, Zhu J, et al. Transplanting mesenchymal stem cells for treatment of ischemic stroke. Cell Transplant. 2018;27(12):1825–34.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Guzman R, Janowski M, Walczak P. Intra-arterial delivery of cell therapies for stroke. Stroke. 2018;49(5):1075–82.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wechsler LR, Bates D, Stroemer P, et al. Cell therapy for chronic stroke. Stroke. 2018;49(5):1066–74.

    Article  PubMed  Google Scholar 

  15. Mays RW, Savitz SI. Intravenous cellular therapies for acute ischemic stroke. Stroke. 2018;49(5):1058–65.

    Article  PubMed  Google Scholar 

  16. Kokaia Z, Darsalia V. Neural stem cell-based therapy for ischemic stroke. Transl Stroke Res. 2011;2(3):272–8.

    Article  PubMed  Google Scholar 

  17. He J, Liu J, Huang Y, et al. Oxidative stress, inflammation, and autophagy: potential targets of mesenchymal stem cells-based therapies in ischemic stroke. Front Neurosci. 2021;15:641157.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Robbins NM, Swanson RA. Opposing effects of glucose on stroke and reperfusion injury: acidosis, oxidative stress, and energy metabolism. Stroke. 2014;45(6):1881–6.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Boshuizen MCS, Steinberg GK. Stem cell-based immunomodulation after stroke: effects on brain repair processes. Stroke. 2018;49(6):1563–70.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kim KA, Shin D, Kim JH, et al. Role of autophagy in endothelial damage and blood-brain barrier disruption in ischemic stroke. Stroke. 2018;49(6):1571–9.

    Article  PubMed  Google Scholar 

  21. Luo T, Park Y, Sun X, et al. Protein misfolding, aggregation, and autophagy after brain ischemia. Transl Stroke Res. 2013;4(6):581–8.

    Article  CAS  PubMed  Google Scholar 

  22. Wechsler LR. Intravenous thrombolytic therapy for acute ischemic stroke. N Engl J Med. 2011;364(22):2138–46.

    Article  CAS  PubMed  Google Scholar 

  23. Pandian JD, Gall SL, Kate MP, et al. Prevention of stroke: a global perspective. Lancet. 2018;392(10154):1269–78.

    Article  PubMed  Google Scholar 

  24. Zerna C, Thomalla G, Campbell BCV, et al. Current practice and future directions in the diagnosis and acute treatment of ischaemic stroke. Lancet. 2018;392(10154):1247–56.

    Article  PubMed  Google Scholar 

  25. Ryu S, Lee SH, Kim SU, et al. Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain. Neural Regen Res. 2016;11(2):298–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hamblin MH, Murad R, Yin J, et al. Modulation of gene expression on a transcriptome-wide level following human neural stem cell transplantation in aged mouse stroke brains. Exp Neurol. 2022;347:113913.

    Article  CAS  PubMed  Google Scholar 

  27. Noh JE, Oh SH, Lee S, et al. Intracerebral transplantation of HLA-homozygous human iPSC-derived neural precursors ameliorates the behavioural and pathological deficits in a rodent model of ischaemic stroke. Cell Prolif. 2020;53(9):e12884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Boese AC, Eckert A, Hamblin MH, et al. Human neural stem cells improve early stage stroke outcome in delayed tissue plasminogen activator-treated aged stroke brains. Exp Neurol. 2020;329:113275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gao J, Bai P, Li Y, et al. Metabolomic profiling of the synergistic effects of ginsenoside Rg1 in combination with neural stem cell transplantation in ischemic stroke rats. J Proteome Res. 2020;19(7):2676–88.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang B, Joseph B, Saatman KE, et al. Intra-arterial delivery of neural stem cells to the Rat and mouse brain: application to cerebral ischemia. J Vis Exp. 2020;(160). https://doi.org/10.3791/61119.

  31. Wang G, Han B, Shen L, et al. Silencing of circular RNA HIPK2 in neural stem cells enhances functional recovery following ischaemic stroke. EBioMedicine. 2020;52:102660.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Korshunova I, Rhein S, García-González D, et al. Genetic modification increases the survival and the neuroregenerative properties of transplanted neural stem cells. JCI Insight. 2020;5(4):e126268.

    Article  PubMed Central  Google Scholar 

  33. Kim J, Shin K, Cha Y, et al. Neuroprotective effects of human neural stem cells over-expressing choline acetyltransferase in a middle cerebral artery occlusion model. J Chem Neuroanat. 2020;103:101730.

    Article  PubMed  Google Scholar 

  34. Kondori BJ, Asadi MH, Bahadoran H, et al. Intra-arterial transplantation of neural stem cells improve functional recovery after transient ischemic stroke in adult rats. Bratisl Lek Listy. 2020;121(1):8–13.

    PubMed  Google Scholar 

  35. Tian L, Zhu W, Liu Y, et al. Neural stem cells transfected with leukemia inhibitory factor promote neuroprotection in a rat model of cerebral ischemia. Neurosci Bull. 2019;35(5):901–8.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wang D, Wang L, Bai L, et al. Effects of mnhibition of miR-155-5p in neural stem cell subarachnoid transplant on rats with cerebral infarction. Hum Gene Ther Methods. 2019;30(5):184–93.

    Article  CAS  PubMed  Google Scholar 

  37. Bernstock JD, Peruzzotti-Jametti L, Leonardi T, et al. SUMOylation promotes survival and integration of neural stem cell grafts in ischemic stroke. EBioMedicine. 2019;42:214–24.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Xu P, Shi X, Zhang X, et al. Overexpression of BRCA1 in neural stem cells enhances cell survival and functional recovery after transplantation into experimental ischemic stroke. Oxid Med Cell Longev. 2019;3(2019):8739730.

    Google Scholar 

  39. Peng JJ, Sha R, Li MX, et al. Repetitive transcranial magnetic stimulation promotes functional recovery and differentiation of human neural stem cells in rats after ischemic stroke. Exp Neurol. 2019;313:1–9.

    Article  CAS  PubMed  Google Scholar 

  40. Zhang JJ, Zhu JJ, Hu YB, et al. Transplantation of bFGF-expressing neural stem cells promotes cell migration and functional recovery in rat brain after transient ischemic stroke. Oncotarget. 2017;8(60):102067–77.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Ziaee SM, Tabeshmehr P, Haider KH, et al. Optimization of time for neural stem cells transplantation for brain stroke in rats. Stem Cell Investig. 2017;14(4):29.

    Article  CAS  Google Scholar 

  42. Augestad IL, Nyman AKG, Costa AI, et al. Effects of neural stem cell and olfactory ensheathing cell co-transplants on tissue remodelling after transient focal cerebral ischemia in the adult rat. Neurochem Res. 2017;42(6):1599–609.

    Article  CAS  PubMed  Google Scholar 

  43. Darsalia V, Allison SJ, Cusulin C, et al. Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain. J Cereb Blood Flow Metab. 2011;31(1):235–42.

    Article  PubMed  Google Scholar 

  44. An Y, Ma X, Lu T, et al. Application of magnetic resonance imaging molecular probe in the treatment of cerebral infarction and paralysis of hind limbs with neural stem cells derived from pluripotent stem cells. World Neurosurg. 2020;138:608–18.

    Article  PubMed  Google Scholar 

  45. Andres RH, Horie N, Slikker W, et al. Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain. Brain. 2011;134(Pt 6):1777–89.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Genet N, Hirschi KK. Understanding neural stem cell regulation in vivo and applying the insights to cell therapy for strokes. Regen Med. 2021;16(9):861–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhang GL, Zhu ZH, et al. Neural stem cell transplantation therapy for brain ischemic stroke: review and perspectives. World J Stem Cells. 2019;11(10):817–30.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Liao LY, Lau BW, Sánchez-Vidaña DI, et al. Exogenous neural stem cell transplantation for cerebral ischemia. Neural Regen Res. 2019;14(7):1129–37.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Rikhtegar R, Yousefi M, Dolati S, et al. Stem cell-based cell therapy for neuroprotection in stroke: a review. J Cell Biochem. 2019;120(6):8849–62.

    Article  CAS  PubMed  Google Scholar 

  50. Baker EW, Kinder HA, West FD. Neural stem cell therapy for stroke: a multimechanistic approach to restoring neurological function. Brain Behav. 2019;9(3):e01214.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Salehi MS, Safari A, Pandamooz S, et al. The beneficial potential of genetically modified stem cells in the treatment of stroke: a review. Stem Cell Rev Rep. 2021;25:1–29.

    Google Scholar 

  52. Lee HJ, Lim IJ, Lee MC, et al. Human neural stem cells genetically modified to overexpress brain-derived neurotrophic factor promote functional recovery and neuroprotection in a mouse stroke model. J Neurosci Res. 2010;88(15):3282–94.

    Article  CAS  PubMed  Google Scholar 

  53. Xie F, Liu H, Liu Y. Adult neurogenesis following ischemic stroke and implications for cell-based therapeutic approaches. World Neurosurg. 2020;138:474–80.

    Article  PubMed  Google Scholar 

  54. Huang L, Zhang L. Neural stem cell therapies and hypoxic-ischemic brain injury. Prog Neurobiol. 2019;173:1–17.

    Article  CAS  PubMed  Google Scholar 

  55. Tuazon JP, Castelli V, Lee JY, et al. Neural stem cells. Adv Exp Med Biol. 2019;1201:79–91.

    Article  CAS  PubMed  Google Scholar 

  56. Ottoboni L, von Wunster B, Martino G. Therapeutic plasticity of neural stem cells. Front Neurol. 2020;20(11):148.

    Article  Google Scholar 

  57. Zhao T, Wang Z, Zhu T, et al. Downregulation of Thbs4 caused by neurogenic niche changes promotes neuronal regeneration after traumatic brain injury. Neurol Res. 2020;42(8):703–11.

    Article  CAS  PubMed  Google Scholar 

  58. Jin K, Wang X, Xie L, et al. Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci U S A. 2006;103(35):13198–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Fan B, Pan W, Wang X, et al. Long noncoding RNA mediates stroke-induced neurogenesis. Stem Cells. 2020;38(8):973–85.

    Article  CAS  PubMed  Google Scholar 

  60. Wang P, Zhang HL, Li W, et al. Generation of patient-specific induced neuronal cells using a direct reprogramming strategy. Stem Cells Dev. 2014;23(1):16–23.

    Article  PubMed  CAS  Google Scholar 

  61. Ye Q, Wu Y, Wu J, et al. Neural stem cells expressing bFGF reduce brain damage and restore sensorimotor function after neonatal hypoxia-ischemia. Cell Physiol Biochem. 2018;45(1):108–18.

    Article  CAS  PubMed  Google Scholar 

  62. Chou CH, Modo M. Characterization of gene expression changes in human neural stem cells and endothelial cells modeling a neurovascular microenvironment. Brain Res Bull. 2020;158:9–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Chen X, Wu H, Chen H, et al. Astragaloside VI promotes neural stem cell proliferation and enhances neurological function recovery in transient cerebral ischemic injury via activating EGFR/MAPK signaling cascades. Mol Neurobiol. 2019;56(4):3053–67.

    Article  CAS  PubMed  Google Scholar 

  64. Li Y, Liu B, Chen Y, et al. Extracellular vesicle application as a novel therapeutic strategy for ischemic stroke. Transl Stroke Res. 2021. https://doi.org/10.1007/s12975-021-00915-3.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Spellicy SE, Kaiser EE, Bowler MM, et al. Neural stem cell extracellular vesicles disrupt midline shift predictive outcomes in porcine ischemic stroke model. Transl Stroke Res. 2020;11(4):776–88.

    Article  CAS  PubMed  Google Scholar 

  66. Webb RL, Kaiser EE, Scoville SL, et al. Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic Stroke Model. Transl Stroke Res. 2018;9(5):530–9.

    Article  CAS  PubMed  Google Scholar 

  67. Corey S, Bonsack B, Heyck M, et al. Harnessing the anti-inflammatory properties of stem cells for transplant therapy in hemorrhagic stroke. Brain Hemorrhages. 2020;1(1):24–33.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Liu F, Lu J, Manaenko A, et al. Mitochondria in ischemic stroke: new insight and implications. Aging Dis. 2018;9(5):924–37.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Andrabi SS, Parvez S, Tabassum H. Ischemic stroke and mitochondria: mechanisms and targets. Protoplasma. 2020;257(2):335–43.

    Article  PubMed  CAS  Google Scholar 

  70. He Z, Ning N, Zhou Q, et al. Mitochondria as a therapeutic target for ischemic stroke. Free Radic Biol Med. 2020;146:45–58.

    Article  CAS  PubMed  Google Scholar 

  71. Yang JL, Mukda S, Chen SD. Diverse roles of mitochondria in ischemic stroke. Redox Biol. 2018;16:263–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lu M, Guo J, Wu B, et al. Mesenchymal ctem cell-mediated mitochondrial transfer: a therapeutic approach for ischemic stroke. Transl Stroke Res. 2021;12(2):212–29.

    Article  PubMed  Google Scholar 

  73. Chen W, Huang J, Hu Y, et al. Mitochondrial transfer as a therapeutic strategy against ischemic stroke. Transl Stroke Res. 2020;11(6):1214–28.

    Article  PubMed  Google Scholar 

  74. Khacho M, Clark A, Svoboda DS, et al. Mitochondrial dynamics impacts stem cell identity and fate decisions by regulating a nuclear transcriptional program. Cell Stem Cell. 2016;19(2):232–47.

    Article  CAS  PubMed  Google Scholar 

  75. Ashford TP, Porter KR. Cytoplasmic components in hepatic cell lysosomes. J Cell Biol. 1962;12(1):198–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Mo Y, Sun Y, Liu K. Autophagy and inflammation in ischemic stroke. Neural Regen Res. 2020;15(8):1388–96.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Yu X, Wang X, Zeng S, et al. Protective effects of primary neural stem cell treatment in ischemic stroke models. Exp Ther Med. 2018;16(3):2219–28.

    PubMed  PubMed Central  Google Scholar 

  78. Wang M, Liang X, Cheng M, et al. Homocysteine enhances neural stem cell autophagy in in vivo and in vitro model of ischemic stroke. Cell Death Dis. 2019;10(8):561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Othman FA, Tan SC. Preconditioning strategies to enhance neural stem cell-based therapy for ischemic stroke. Brain Sci. 2020;10(11):893.

    Article  CAS  PubMed Central  Google Scholar 

  80. Sandvig I, Gadjanski I, Vlaski-Lafarge M, et al. Strategies to enhance implantation and survival of stem cells after their injection in ischemic neural tissue. Stem Cells Dev. 2017;26(8):554–65.

    Article  CAS  PubMed  Google Scholar 

  81. Singh M, Pandey PK, Bhasin A, et al. Application of stem cells in stroke: a multifactorial approach. Front Neurosci. 2020;9(14):473.

    Article  CAS  Google Scholar 

  82. Bliss TM, Andres RH, Steinberg GK. Optimizing the success of cell transplantation therapy for stroke. Neurobiol Dis. 2010;37(2):275–83.

    Article  PubMed  Google Scholar 

  83. Wei N, Sun Z, Yu J, et al. Immunological responses to transgene-modified neural stem cells after transplantation. Front Immunol. 2021;12:697203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kang P, Kumar S, Schaffer D. Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies. Curr Opin Biomed Eng. 2017;4:13–20.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Wilson KL, Carmichael ST, Segura T. Injection of hydrogel biomaterial scaffolds to The brain after stroke. J Vis Exp. 2020;(164):https://doi.org/10.3791/61450

  86. Moshayedi P, Nih LR, Llorente IL, et al. Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. Biomaterials. 2016;105:145–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wang H, Yang H, Shi Y, et al. Reconstituting neurovascular unit with primary neural stem cells and brain microvascular endothelial cells in three-dimensional matrix. Brain Pathol. 2021;31(5):e12940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Gopalakrishnan A, Shankarappa SA, Rajanikant GK. Hydrogel ccaffolds: towards restitution of ischemic stroke-injured brain. Transl Stroke Res. 2019;10(1):1–18.

    Article  CAS  PubMed  Google Scholar 

  89. Zhang G, Li Y, Reuss JL, et al. Stable intracerebral transplantation of neural stem cells for the treatment of paralysis due to ischemic stroke. Stem Cells Transl Med. 2019;8(10):999–1007.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Zhang G, Cunningham M, Zhang H, et al. First human trial of stem cell transplantation in complex arrays for stroke patients using the intracerebral microinjection instrument. Oper Neurosurg (Hagerstown). 2020;18(5):503–10.

    Article  Google Scholar 

  91. Kalladka D, Sinden J, Pollock K, et al. Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study. Lancet. 2016;388(10046):787–96.

    Article  PubMed  Google Scholar 

  92. Sinden JD, Hicks C, Stroemer P, et al. Human neural stem cell therapy for chronic ischemic stroke: charting progress from laboratory to patients. Stem Cells Dev. 2017;26(13):933–47.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Muir KW, Bulters D, Willmot M, et al. Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2). J Neurol Neurosurg Psychiatry. 2020;91(4):396–401.

    Article  PubMed  Google Scholar 

  94. He JQ, Sussman ES, Steinberg GK. Revisiting stem cell-based clinical trials for ischemic stroke. Front Aging Neurosci. 2020;12:575990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Qiao LY, Huang FJ, Zhao M, et al. A two-year follow-up study of cotransplantation with neural stem/progenitor cells and mesenchymal stromal cells in ischemic stroke patients. Cell Transplant. 2014;23 Suppl 1:S65-72.

    Article  PubMed  Google Scholar 

  96. Kawabori M, Shichinohe H, Kuroda S, et al. Clinical trials of stem cell therapy for cerebral ischemic stroke. Int J Mol Sci. 2020;21(19):7380.

    Article  CAS  PubMed Central  Google Scholar 

  97. Kokaia Z, Darsalia V. Human neural stem cells for ischemic stroke treatment. Results Probl Cell Differ. 2018;66:249–63.

    Article  CAS  PubMed  Google Scholar 

  98. Liu H, Reiter S, Zhou X, et al. Insight into the mechanisms and the challenges on stem cell-Based therapies for cerebral ischemic stroke. Front Cell Neurosci. 2021;15:637210.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Zhang S, Lachance BB, Moiz B, et al. Optimizing stem cell therapy after ischemic brain injury. J Stroke. 2020;22(3):286–305.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Hamblin MH, Lee JP. Neural stem cells for early ischemic stroke. Int J Mol Sci. 2021;22(14):7703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Boese AC, Le QE, Pham D, et al. Neural stem cell therapy for subacute and chronic ischemic stroke. Stem Cell Res Ther. 2018;9(1):154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by grants (2018YFA0107900, 92168103, 32171417, and 2019CXJQ01) from Ministry of Science and Technology of China, National Nature Science Foundation, and Shanghai Municipal Government Peak Disciplines (Type IV) of Institutions of Higher Learning in Shanghai.

Author information

Author notes

  1. Tong Zhao and Tongming Zhu and Liqian Xie contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian Province, China

    Tong Zhao

  2. Fudan University Huashan Hospital, Department of Neurosurgery, National Center for Neurological Disorders, National Key Laboratory for Medical Neurobiology, Shanghai Key Laboratory of Brain Function and Regeneration, Institutes of Brain Science, MOE Frontiers Center for Brain Science, Shanghai Medical College-Fudan University, No.12 Middle Wulumuqi Road, Shanghai, 200040, China

    Tongming Zhu, Liqian Xie, Rong Xie, Feng Xu, Hailiang Tang & Jianhong Zhu

  3. Med-X Research Institute, Shanghai Jiaotong University, Shanghai, 200030, China

    Yao Li

Authors
  1. Tong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tongming Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liqian Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rong Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Feng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hailiang Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jianhong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Feng Xu, Hailiang Tang or Jianhong Zhu.

Ethics declarations

Conflict of interest

None.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, T., Zhu, T., Xie, L. et al. Neural Stem Cells Therapy for Ischemic Stroke: Progress and Challenges. Transl. Stroke Res. 13, 665–675 (2022). https://doi.org/10.1007/s12975-022-00984-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-022-00984-y

Keywords

Search

Navigation