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Bone marrow stromal cells as a therapeutic treatment for ischemic stroke

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Abstract

Cerebral ischemia remains the most frequent cause of death and quality-of-life impairments due to neurological deficits, and accounts for the majority of total healthcare costs. However, treatments for cerebral ischemia are limited. Over the last decade, bone marrow stromal cell (BMSC) therapy has emerged as a particularly appealing option, as it is possible to help patients even when initiated days or even weeks after the ischemic insult. BMSCs are a class of multipotent, self-renewing cells that give rise to differentiated progeny when implanted into appropriate tissues. Therapeutic effects of BMSC treatment for ischemic stroke, including sensory and motor recovery, have been reported in pre-clinical studies and clinical trials. In this article, we review the recent progress in BMSC-based therapy for ischemic stroke, focusing on the route of delivery and pre-processing of BMSCs. Selecting an optimal delivery route is of particular importance. The ideal approach, as well as the least risky, for translational applications still requires further identification. Appropriate preprocessing of BMSCs or combination therapy has the benefit of achieving the maximum possible restoration. Further pre-clinical studies are required to determine the time-window for transplantation and the appropriate dosage of cells.

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References

  1. Chang YC, Shyu WC, Lin SZ, Li H. Regenerative therapy for stroke. Cell Transplant 2007, 16: 171–181.

    PubMed  Google Scholar 

  2. Deng W, Obrocka M, Fischer I, Prockop DJ. In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun 2001, 282: 148–152.

    Article  CAS  PubMed  Google Scholar 

  3. Jaiswal RK, Jaiswal N, Bruder SP, Mbalaviele G, Marshak DR, Pittenger MF. Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J Biol Chem 2000, 275: 9645–9652.

    Article  CAS  PubMed  Google Scholar 

  4. Tang Y, Yasuhara T, Hara K, Matsukawa N, Maki M, Yu G, et al. Transplantation of bone marrow-derived stem cells: a promising therapy for stroke. Cell Transplant 2007, 16: 159–169.

    PubMed  Google Scholar 

  5. Li Y, Chen J, Wang L, Lu M, Chopp M. Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 2001, 56: 1666–1672.

    Article  CAS  PubMed  Google Scholar 

  6. Woodbury D, Reynolds K, Black IB. Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res 2002, 69: 908–917.

    Article  CAS  PubMed  Google Scholar 

  7. Fukuda K. Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering. Artif Organs 2001, 25: 187–193.

    Article  CAS  PubMed  Google Scholar 

  8. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999, 284: 143–147.

    Article  CAS  PubMed  Google Scholar 

  9. Chen JR, Cheng GY, Sheu CC, Tseng GF, Wang TJ, Huang YS. Transplanted bone marrow stromal cells migrate, differentiate and improve motor function in rats with experimentally induced cerebral stroke. J Anat 2008, 213: 249–258.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Nezhadi A, Ghazi F, Rassoli H, Bakhtiari M, Ataiy Z, Soleimani S, et al. BMSC and CoQ10 improve behavioural recovery and histological outcome in rat model of Parkinson’s disease. Pathophysiology 2011, 18: 317–324.

    Article  CAS  PubMed  Google Scholar 

  11. Zacharek A, Shehadah A, Chen J, Cui X, Roberts C, Lu M, et al. Comparison of bone marrow stromal cells derived from stroke and normal rats for stroke treatment. Stroke 2010, 41: 524–530.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Guo F, Lv S, Lou Y, Tu W, Liao W, Wang Y, et al. Bone marrow stromal cells enhance the angiogenesis in ischaemic cortex after stroke: involvement of notch signalling. Cell Biol Int 2012, 36: 997–1004.

    Article  CAS  PubMed  Google Scholar 

  13. Yoo SW, Kim SS, Lee SY, Lee HS, Kim HS, Lee YD, et al. Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model. Exp Mol Med 2008, 40: 387–397.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu YX, et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 2000, 20: 1311–1319.

    Article  CAS  PubMed  Google Scholar 

  15. Borlongan CV, Lind JG, Dillon-Carter O, Yu G, Hadman M, Cheng C, et al. Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats. Brain Res 2004, 1010: 108–116.

    Article  CAS  PubMed  Google Scholar 

  16. Shen LH, Li Y, Chen J, Zhang J, Vanguri P, Borneman J, et al. Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 2006, 137: 393–399.

    Article  CAS  PubMed  Google Scholar 

  17. Liu N, Deguchi K, Yamashita T, Liu W, Ikeda Y, Abe K. Intracerebral transplantation of bone marrow stromal cells ameliorates tissue plasminogen activator-induced brain damage after cerebral ischemia in mice detected by in vivo and ex vivo optical imaging. J Neurosci Res 2012, 90: 2086–2093.

    Article  CAS  PubMed  Google Scholar 

  18. Liu N, Chen R, Du H, Wang J, Zhang Y, Wen J. Expression of IL-10 and TNF-alpha in rats with cerebral infarction after transplantation with mesenchymal stem cells. Cell Mol Immunol 2009, 6: 207–213.

    Article  PubMed  Google Scholar 

  19. Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 2002, 174: 11–20.

    Article  PubMed  Google Scholar 

  20. Irons H, Lind JG, Wakade CG, Yu G, Hadman M, Carroll J, et al. Intracerebral xenotransplantation of GFP mouse bone marrow stromal cells in intact and stroke rat brain: graft survival and immunologic response. Cell Transplant 2004, 13: 283–294.

    Article  CAS  PubMed  Google Scholar 

  21. Shichinohe H, Kuroda S, Lee JB, Nishimura G, Yano S, Seki T, et al. In vivo tracking of bone marrow stromal cells transplanted into mice cerebral infarct by fluorescence optical imaging. Brain Res Brain Res Protoc 2004, 13: 166–175.

    Article  PubMed  Google Scholar 

  22. Chen J, Li Y, Wang L, Lu M, Zhang X, Chopp M. Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. J Neurol Sci 2001, 189: 49–57.

    Article  CAS  PubMed  Google Scholar 

  23. Miyamoto M, Kuroda S, Zhao S, Magota K, Shichinohe H, Houkin K, et al. Bone marrow stromal cell transplantation enhances recovery of local glucose metabolism after cerebral infarction in rats: a serial 18F-FDG PET study. J Nucl Med 2013, 54: 145–150.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang C, Li Y, Chen J, Gao Q, Zacharek A, Kapke A, et al. Bone marrow stromal cells upregulate expression of bone morphogenetic proteins 2 and 4, gap junction protein connexin-43 and synaptophysin after stroke in rats. Neuroscience 2006, 141: 687–695.

    Article  CAS  PubMed  Google Scholar 

  25. Keimpema E, Fokkens MR, Nagy Z, Agoston V, Luiten PG, Nyakas C, et al. Early transient presence of implanted bone marrow stem cells reduces lesion size after cerebral ischaemia in adult rats. Neuropathol Appl Neurobiol 2009, 35: 89–102.

    Article  CAS  PubMed  Google Scholar 

  26. Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001, 32: 1005–1011.

    Article  CAS  PubMed  Google Scholar 

  27. Wang L, Li Y, Chen J, Gautam SC, Zhang Z, Lu M, et al. Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture. Exp Hematol 2002, 30: 831–836.

    Article  CAS  PubMed  Google Scholar 

  28. Chen J, Zhang ZG, Li Y, Wang L, Xu YX, Gautam SC, et al. Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 2003, 92: 692–699.

    Article  CAS  PubMed  Google Scholar 

  29. Chen J, Li Y, Zhang R, Katakowski M, Gautam SC, Xu Y, et al. Combination therapy of stroke in rats with a nitric oxide donor and human bone marrow stromal cells enhances angiogenesis and neurogenesis. Brain Res 2004, 1005: 21–28.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang J, Li Y, Chen J, Yang M, Katakowski M, Lu M, et al. Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells. Brain Res 2004, 1030: 19–27.

    Article  CAS  PubMed  Google Scholar 

  31. Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab 2013, 33 (11): 1711–1715.

    Article  Google Scholar 

  32. Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D, et al. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 2003, 73: 778–786.

    Article  CAS  PubMed  Google Scholar 

  33. Okazaki T, Magaki T, Takeda M, Kajiwara Y, Hanaya R, Sugiyama K, et al. Intravenous administration of bone marrow stromal cells increases survivin and Bcl-2 protein expression and improves sensorimotor function following ischemia in rats. Neurosci Lett 2008, 430: 109–114.

    Article  CAS  PubMed  Google Scholar 

  34. Zheng W, Honmou O, Miyata K, Harada K, Suzuki J, Liu H, et al. Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia. Brain Res 2010, 1310: 8–16.

    Article  CAS  PubMed  Google Scholar 

  35. Kawabori M, Kuroda S, Ito M, Shichinohe H, Houkin K, Kuge Y, et al. Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct. Neuropathology 2013, 33: 140–148.

    Article  PubMed  Google Scholar 

  36. Jang DK, Park SI, Han YM, Jang KS, Park MS, Chung YA, et al. Motor-evoked potential confirmation of functional improvement by transplanted bone marrow mesenchymal stem cell in the ischemic rat brain. J Biomed Biotechnol 2011, 2011: 238409.

    PubMed Central  PubMed  Google Scholar 

  37. Bliss TM, Andres RH, Steinberg GK. Optimizing the success of cell transplantation therapy for stroke. Neurobiol Dis 2010, 37: 275–283.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Wu J, Sun Z, Sun HS, Weisel RD, Keating A, Li ZH, et al. Intravenously administered bone marrow cells migrate to damaged brain tissue and improve neural function in ischemic rats. Cell Transplant 2008, 16: 993–1005.

    Article  PubMed  Google Scholar 

  39. Fischer UM, Harting MT, Jimenez F, Monzon-Posadas WO, Xue H, Savitz SI, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev 2009, 18: 683–692.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Honma T, Honmou O, Iihoshi S, Harada K, Houkin K, Hamada H, et al. Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Exp Neurol 2006, 199: 56–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Li Y, McIntosh K, Chen J, Zhang C, Gao Q, Borneman J, et al. Allogeneic bone marrow stromal cells promote glial-axonal remodeling without immunologic sensitization after stroke in rats. Exp Neurol 2006, 198: 313–325.

    Article  CAS  PubMed  Google Scholar 

  42. Shen LH, Li Y, Chen J, Zacharek A, Gao Q, Kapke A, et al. Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke. J Cereb Blood Flow Metab 2007, 27 (1): 6–13.

    Article  Google Scholar 

  43. Pavlichenko N, Sokolova I, Vijde S, Shvedova E, Alexandrov G, Krouglyakov P, et al. Mesenchymal stem cells transplantation could be beneficial for treatment of experimental ischemic stroke in rats. Brain Res 2008, 1233: 203–213.

    Article  CAS  PubMed  Google Scholar 

  44. Omori Y, Honmou O, Harada K, Suzuki J, Houkin K, Kocsis JD. Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats. Brain Res 2008, 1236: 30–38.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Gopurappilly R, Pal R, Mamidi MK, Dey S, Bhonde R, Das AK. Stem cells in stroke repair: current success and future prospects. CNS Neurol Disord Drug Targets 2011, 10: 741–756.

    Article  CAS  PubMed  Google Scholar 

  46. Ikeda N, Nonoguchi N, Zhao MZ, Watanabe T, Kajimoto Y, Furutama D, et al. Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats. Stroke 2005, 36: 2725–2730.

    Article  CAS  PubMed  Google Scholar 

  47. Zhao MZ, Nonoguchi N, Ikeda N, Watanabe T, Furutama D, Miyazawa D, et al. Novel therapeutic strategy for stroke in rats by bone marrow stromal cells and ex vivo HGF gene transfer with HSV-1 vector. J Cereb Blood Flow Metab 2006, 26: 1176–1188.

    Article  CAS  PubMed  Google Scholar 

  48. Hokari M, Kuroda S, Chiba Y, Maruichi K, Iwasaki Y. Synergistic effects of granulocyte-colony stimulating factor on bone marrow stromal cell transplantation for mice cerebral infarct. Cytokine 2009, 46: 260–266.

    Article  CAS  PubMed  Google Scholar 

  49. Nomura T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. I.V. infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Neuroscience 2005, 136: 161–169.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Horita Y, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat. J Neurosci Res 2006, 84: 1495–1504.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Liu H, Honmou O, Harada K, Nakamura K, Houkin K, Hamada H, et al. Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia. Brain 2006, 129: 2734–2745.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Onda T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia. J Cereb Blood Flow Metab 2008, 28: 329–340.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Mimura T, Dezawa M, Kanno H, Yamamoto I. Behavioral and histological evaluation of a focal cerebral infarction rat model transplanted with neurons induced from bone marrow stromal cells. J Neuropathol Exp Neurol 2005, 64: 1108–1117.

    Article  PubMed  Google Scholar 

  54. Wei L, Rovainen CM, Woolsey TA. Ministrokes in rat barrel cortex. Stroke 1995, 26: 1459–1462.

    Article  CAS  PubMed  Google Scholar 

  55. Song M, Mohamad O, Gu X, Wei L, Yu SP. Restoration of intracortical and thalamocortical circuits after transplantation of bone marrow mesenchymal stem cells into the ischemic brain of mice. Cell Transplant 2013, 22 (11): 2001–2015.

    Article  Google Scholar 

  56. Wei N, Yu SP, Gu X, Taylor TM, Song D, Liu XF, et al. Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice. Cell Transplant 2013, 22: 977–991.

    Article  PubMed  Google Scholar 

  57. Chen C, Cheng Y, Chen J. Transfection of Noggin in bone marrow stromal cells (BMSCs) enhances BMSC-induced functional outcome after stroke in rats. J Neurosci Res 2011, 89: 1194–1202.

    Article  CAS  PubMed  Google Scholar 

  58. Yu X, Chen D, Zhang Y, Wu X, Huang Z, Zhou H, et al. Overexpression of CXCR4 in mesenchymal stem cells promotes migration, neuroprotection and angiogenesis in a rat model of stroke. J Neurol Sci 2012, 316: 141–149.

    Article  CAS  PubMed  Google Scholar 

  59. Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, et al. Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 2002, 59: 514–523.

    Article  CAS  PubMed  Google Scholar 

  60. Toyama K, Honmou O, Harada K, Suzuki J, Houkin K, Hamada H, et al. Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia. Exp Neurol 2009, 216: 47–55.

    Article  CAS  PubMed  Google Scholar 

  61. Krause C, Guzman A, Knaus P. Noggin. Int J Biochem Cell Biol 2011, 43: 478–481.

    Article  CAS  PubMed  Google Scholar 

  62. Ding J, Cheng Y, Gao S, Chen J. Effects of nerve growth factor and Noggin-modified bone marrow stromal cells on stroke in rats. J Neurosci Res 2011, 89: 222–230.

    Article  CAS  PubMed  Google Scholar 

  63. Francis KR, Wei L. Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning. Cell Death Dis 2010, 1: e22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Wei L, Fraser JL, Lu ZY, Hu X, Yu SP. Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats. Neurobiol Dis 2012, 46: 635–645.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Wang Y, Huang J, Li Y, Yang GY. Roles of chemokine CXCL12 and its receptors in ischemic stroke. Curr Drug Targets 2012, 13: 166–172.

    Article  CAS  PubMed  Google Scholar 

  66. Wang Y, Deng Y, Zhou GQ. SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model. Brain Res 2008, 1195: 104–112.

    Article  CAS  PubMed  Google Scholar 

  67. Chen J, Li Y, Wang L, Lu M, Chopp M. Caspase inhibition by Z-VAD increases the survival of grafted bone marrow cells and improves functional outcome after MCAo in rats. J Neurol Sci 2002, 199: 17–24.

    Article  CAS  PubMed  Google Scholar 

  68. Cui X, Chen J, Zacharek A, Li Y, Roberts C, Kapke A, et al. Nitric oxide donor upregulation of stromal cell-derived factor-1/chemokine (CXC motif) receptor 4 enhances bone marrow stromal cell migration into ischemic brain after stroke. Stem Cells 2007, 25: 2777–2785.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. Cui X, Chen J, Zacharek A, Roberts C, Savant-Bhonsale S, Chopp M. Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization. Neuroscience 2008, 156: 155–164.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Shyu WC, Lin SZ, Yen PS, Su CY, Chen DC, Wang HJ, et al. Stromal cell-derived factor-1 alpha promotes neuroprotection, angiogenesis, and mobilization/homing of bone marrow-derived cells in stroke rats. J Pharmacol Exp Ther 2008, 324: 834–849.

    Article  CAS  PubMed  Google Scholar 

  71. Zhao Y, Guan Y, Xu Y, Li Y, Wu W. Sodium Ferulate combined with bone marrow stromal cell treatment ameliorating rat brain ischemic injury after stroke. Brain Res 2012, 1450: 157–165.

    Article  CAS  PubMed  Google Scholar 

  72. Osanai T, Kuroda S, Yasuda H, Chiba Y, Maruichi K, Hokari M, et al. Noninvasive transplantation of bone marrow stromal cells for ischemic stroke: preliminary study with a thermoreversible gelation polymer hydrogel. Neurosurgery 2010, 66: 1140–1147; discussion 1147.

    Article  PubMed  Google Scholar 

  73. Pirzad Jahromi G, Seidi S, Sadr SS, Shabanzadeh AP, Keshavarz M, Kaka GR, et al. Therapeutic effects of a combinatorial treatment of simvastatin and bone marrow stromal cells on experimental embolic stroke. Basic Clin Pharmacol Toxicol 2012, 110: 487–493.

    Article  CAS  PubMed  Google Scholar 

  74. Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 2005, 57: 874–882.

    Article  PubMed  Google Scholar 

  75. Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 2010, 28: 1099–1106.

    Article  PubMed  Google Scholar 

  76. Kondziolka D, Steinberg GK, Wechsler L, Meltzer CC, Elder E, Gebel J, et al. Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg 2005, 103: 38–45.

    Article  PubMed  Google Scholar 

  77. Battistella V, de Freitas GR, da Fonseca LM, Mercante D, Gutfilen B, Goldenberg RC, et al. Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke. Regen Med 2011, 6: 45–52.

    Article  CAS  PubMed  Google Scholar 

  78. Moniche F, Gonzalez A, Gonzalez-Marcos JR, Carmona M, Pinero P, Espigado I, et al. Intra-arterial bone marrow mononuclear cells in ischemic stroke: a pilot clinical trial. Stroke 2012, 43: 2242–2244.

    Article  PubMed  Google Scholar 

  79. Friedrich MA, Martins MP, Araujo MD, Klamt C, Vedolin L, Garicochea B, et al. Intra-arterial infusion of autologous bone marrow mononuclear cells in patients with moderate to severe middle cerebral artery acute ischemic stroke. Cell Transplant 2012, 21Suppl 1: S13–21.

    Article  PubMed  Google Scholar 

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Correspondence to Yujun Pan.

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Yang, Z., Zhu, L., Li, F. et al. Bone marrow stromal cells as a therapeutic treatment for ischemic stroke. Neurosci. Bull. 30, 524–534 (2014). https://doi.org/10.1007/s12264-013-1431-y

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