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Intra-arterial Approaches to Stem Cell Therapy for Ischemic Stroke

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Cell Therapy for Brain Injury

Abstract

Stroke remains the leading cause of disability and among the top five causes of death around the world. While recanalization therapies, first approved about two decades ago for ischemic stroke, have changed the nihilistic approach that prevailed in the past, their impact remains small. Hence, there is a critical need to translate novel stroke therapies to reduce the burden of ischemic stroke. There is a strong biologic rationale for cell-based therapy with a variety of stem cells in ischemic stroke, given that the brain’s repair process after stroke is driven by endogenous stem cells. Over the last 15 years, numerous preclinical studies of cell-based therapy for ischemic stroke show consistent promise of safety and efficacy. While these studies utilize a variety of cells and different routes of cell administration, the intra-arterial route of cell delivery has several attractive clinical attributes including minimally invasive and targeted delivery of cells to area of brain injury. This route of delivery of cells has been the focus of our laboratory and here we review the preclinical data and the recent rise in published early clinical trials of cell-based therapy in ischemic stroke. These clinical trial data in their sum total suggest robust safety of this approach and set the stage for the next phase of clinical trials to establish its clinical efficacy in this devastating disease.

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References

  1. Hacke W, Donnan G, Fieschi C, Kaste M, Kummer R von, Broderick JP, Brott T, Frankel M, Grotta JC, et al. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. The Lancet. 2004;363:768–74.

    Google Scholar 

  2. Lansberg MG, Schrooten M, Bluhmki E, et al. Treatment time-specific number needed to treat estimates for tissue plasminogen activator therapy in acute stroke based on shifts over the entire range of the modified Rankin Scale. Stroke. 2009;40:2079–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Kleindorfer D, Lindsell CJ, Brass L, Koroshetz W, Broderick JP. National US estimates of recombinant tissue plasminogen activator use: ICD-9 codes substantially underestimate. Stroke. 2008;39:924–8.

    Article  PubMed  Google Scholar 

  4. Macrae IM. Preclinical stroke research—advantages and disadvantages of the most common rodent models of focal ischaemia. Br J Pharmacol. 2011;164:1062–78.

    Google Scholar 

  5. Berkhemer OA, Dippel DW and MR CLEAN Investigators. A randomized trial of intra-arterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11–20. doi: 10. 1056/NEJMoa1411587. Epub 2014 Dec 17.

    Google Scholar 

  6. Dippel D, et al. 9th World Stroke Congress: Session: Main Theme 43: Late Breaking News. No abstract number. Presented October 25, 2014.

    Google Scholar 

  7. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci. 1999 Sep;22(9):391–7. (Review).

    Google Scholar 

  8. Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol. 2007;6:182–7.

    Google Scholar 

  9. Taylor TN, Davis PH, Torner JC, et al. Lifetime cost of stroke in the United States. Stroke. 1996;27:1459–66.

    Article  CAS  PubMed  Google Scholar 

  10. Li Y, Chen J, Wang L, Lu M, Chopp M. Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology. 2001;56:1666–72.

    Article  CAS  PubMed  Google Scholar 

  11. Shen LH, Li Y, Chen J, Zhang J, Vanguri P, Borneman J, Chopp M. Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience. 2006;137:393–9.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang ZG, Chopp M. Neurorestorative therapies for stroke: underlying mechanisms and translation to the clinic. Lancet Neurol. 2009;8:491–500.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Baker AH, Sica V, Work LM, et al. Brain protection using autologous bone marrow cell metalloproteinase inhibitors, and metabolic treatment in cerebral ischemia. Proc Natl Acad Sci USA. 2007;104:3597–602.

    Google Scholar 

  14. Shen LH, Li Y, Chen J, et al. One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke. Stroke. 2007;38:2150–56.

    Article  PubMed  Google Scholar 

  15. Kamiya N, Ueda M, Igarashi H, et al. Intra-arterial trans- plantation of bone marrow mononuclear cells immediately after reperfusion decreases brain injury after focal ischemia in rats. Life Sci. 2008;83:433–7.

    Article  CAS  PubMed  Google Scholar 

  16. Chung DJ, Choi CB, Lee SH, Kang EH, Lee JH, Hwang SH, Han H, Lee JH, Choe BY, Lee SY, Kim HY. Intraarterially delivered human umbilical cord blood-derived mesenchymal stem cells in canine cerebral ischemia. J Neurosci Res. 2009 Dec;87(16):3554–67.

    Google Scholar 

  17. Gutierrez-Fernandez M, Rodriguez-Frutos B, Alvarez-Grech J, et al. Functional recoveryafter hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke inrats. Neuroscience. 2011;175:394–405.

    Google Scholar 

  18. Lu SS, Liu S, Zu QQ, Xu XQ, Yu J, Wang JW, Zhang Y, Shi HB. In vivo MR imaging of intraarterially delivered magnetically labeled mesenchymal stem cells in a canine stroke model. PLoS ONE. 2013;8(2):e54963.

    Google Scholar 

  19. Ishizaka S, Horie N, Satoh K, Fukuda Y, Nishida N, Nagata I. Intra-arterial cell transplantation provides timing-dependent cell distribution and functional recovery after stroke. Stroke. 2013;44:720–6.

    Google Scholar 

  20. Jiang W, Liang G, Li X, Li Z, Gao X, Feng S, et al. Intracarotid transplantation of autologous adipose-derived mesenchymal stem cells significantly improves neurological deficits in rats after MCAo. J Mater Sci Mater Med. 2014;25:1357–66.

    Article  CAS  PubMed  Google Scholar 

  21. Du S, Guan J, Mao G, Liu Y, Ma S, Bao X, Gao J, Feng M, Li G, Ma W, Yang Y, Zhao RC, Wang R. Intra-arterial delivery of human bone marrow mesenchymal stem cells is a safe and effective way to treat cerebral ischemia in rats. Cell Transplant. 2014 Nov 4;23(suppl 1):73–82.

    Google Scholar 

  22. Yavagal DR, Lin B, Raval AP, Garza PS, Dong C, et al. Efficacy and dose-dependent safety of intra-arterial delivery of mesenchymal stem cells in a rodent stroke model. PLoS ONE. 2014;9(5):e93735.

    Article  Google Scholar 

  23. Weissman IL, Anderson DJ, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol. 2001;17:387–403. (Review).

    Article  CAS  PubMed  Google Scholar 

  24. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science. 1998 Nov 6;282(5391):1145–7.

    Article  CAS  PubMed  Google Scholar 

  25. Burns TC, Steinberg GK. Stem cells and stroke: opportunities, challenges and strategies. Expert Opin Biol Ther. 2011 Apr;11(4):447–61. doi: 10.1517/14712598.2011.552883. Epub 2011 Feb 16. Review.

    Google Scholar 

  26. Zhang C, Li Y, Chen J, et al. Bone marrow stromal cells upregulate expression of bonemorphogenetic proteins 2 and 4, gap junction protein connexin-43 and synaptophysin after stroke _ in rats. Neuroscience. 2006;141:687–95.

    Article  CAS  PubMed  Google Scholar 

  27. Leong WK, Lewis MD, Koblar SA. Concise review: Preclinical studies on human cell-based therapy in rodent ischemic stroke models: where are we now after a decade? Stem Cells. 2013;31(6):1040–3.

    Google Scholar 

  28. Vu Q, Xie K, Eckert M, Zhao W, Cramer SC. Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke. Neurology. 2014 Mar 7;82(14):1277–86.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Eckert MA, Vu Q, Xie K, Yu J, Liao W, Cramer SC, Zhao W. Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke. J Cereb Blood Flow Metab. 2013 Sep;33(9):1322–34.

    Google Scholar 

  30. Gutiérrez-Fernández M, Rodríguez-Frutos B, Ramos-Cejudo J, Teresa Vallejo-CremadesM, Fuentes B, Cerdán S, Díez-Tejedor E. Effects of intravenous administration of allogenic bone marrow- and adipose tissue-derived mesenchymal stem cells on functional recovery and brain repair markers in experimental ischemic stroke. Stem Cell Res Ther. 2013;4(1):11.

    Google Scholar 

  31. Kranz A, Wagner DC, Kamprad M, et al. Transplantation of placenta-derived mesenchymal stromal cells upon experimental stroke in rats. Brain Res. 2010;1315:128–36.

    Article  CAS  PubMed  Google Scholar 

  32. Leong WK, Henshall TL, Arthur A, Kremer KL, Lewis MD, Helps SC, Field J, Hamilton-Bruce MA, Warming S, Manavis J, Vink R, Gronthos S, Koblar SA. Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms. Stem Cells Transl Med. 2012 Mar;1(3):177–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Burns TC, Verfaillie CM, Low WC. Stem cells for ischemic brain injury: a critical review. J Comp Neurol. 2009;515(1):125–44.

    Google Scholar 

  34. Rosado-de-Castro PH, Schmidt Fda R, Battistella V, Lopes de Souza SA, Gutfilen B, Goldenberg RC, Kasai-Brunswick TH, Vairo L, Silva RM, Wajnberg E, Alvarenga Americano do Brasil PE, Gasparetto EL, Maiolino A, Alves-Leon SV, Andre C, Mendez-Otero R, Rodriguez de Freitas G, Barbosa da Fonseca LM. Biodistribution of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients. Regen Med. 2013a;8(2):145–55. doi:10.2217/rme.13.2.

    Article  Google Scholar 

  35. Chen FM, Wu LA, Zhang M, Zhang R, Sun HH. Homing of endogenous stem/progenitor cells for in situ tissue regeneration: promises, strategies, and translational perspectives. Biomaterials. 2011;32(12):3189–209.

    Google Scholar 

  36. Chavakis E, Urbich C, Dimmeler S. Homing and engraftment of progenitor cells: a prerequisite for cell therapy. J Mol Cell Cardiol. 2008;45(4):514–22.

    Google Scholar 

  37. Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ. Stromal cell-derived factor-1α plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation. 2004;110(21):3300–5.

    Google Scholar 

  38. Belema-Bedada F, Uchida S, Martire A, Kostin S, Braun T. Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2. Cell Stem Cell. 2008;2(6):566–75.

    Article  CAS  PubMed  Google Scholar 

  39. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858–864. (One of the first reports that recruitment of CXCR4-positive progenitor cells to regenerating tissues is mediated by hypoxic gradients via HIF-1-induced expression of SDF–1).

    Google Scholar 

  40. Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cell-derived factor-1α enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthase-related pathway: next-generation chemokine therapy for therapeutic neovascularization. Circulation. 2004;109(20):2454–61.

    Google Scholar 

  41. Kim SJ, Moon GJ, Cho YH, Kang HY, Hyung NK, Kim D, Lee JH, Nam JY, Bang OY. Circulating mesenchymal stem cells microparticles in patients with cerebrovascular disease. PLoS ONE. 2012;7(5):e37036.

    Google Scholar 

  42. Youn SW, Lee SW, Lee J, et al. COMP-Ang1 stimulates HIF-1α-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment. Blood. 2011;117(16):4376–86.

    Article  CAS  PubMed  Google Scholar 

  43. Heissig B, Hattori K, Dias S, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109(5):625–37.

    Google Scholar 

  44. Kaminski A, Ma N, Donndorf P, et al. Endothelial NOS is required for SDF-1α/CXCR4-mediated peripheral endothelial adhesion of c-kit+ bone marrow stem cells. Lab Invest. 2008;88(1):58–69.

    Article  CAS  PubMed  Google Scholar 

  45. Li N, Lu X, Zhao X, et al. Endothelial nitric oxide synthase promotes bone marrow stromal cell migration to the ischemic myocardium via upregulation of stromal cell-derived factor-1alpha. Stem Cells. 2009;27(4):961–70.

    Article  CAS  PubMed  Google Scholar 

  46. Hattori K, Dias S, Heissig B, et al. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J Exp Med. 2001;193(9):1005–14.

    Google Scholar 

  47. Hopkins SP, Bulgrin JP, Sims RL, Bowman B, Donovan DL, Schmidt SP. Controlled delivery of vascular endothelial growth factor promotes neovascularization and maintains limb function in a rabbit model of ischemia. J Vasc Surg. 1998;27(5):886–4. (discussion 895).

    Google Scholar 

  48. Levesque JP, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest. 2003;111(2):187–96.

    Google Scholar 

  49. Pitchford SC, Furze RC, Jones CP, Wengner AM, Rankin SM. Differential mobilization of subsets of progenitor cells from the bone marrow. Cell Stem Cell. 2009;4(1):62–72.

    Article  CAS  PubMed  Google Scholar 

  50. Guzman R, Uchida N, Bliss TM, He D, Christopherson KK, Stellwagen D, Capela A, Greve J, Malenka RC, et al. Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci. 2007;104:10211–16. (USA).

    Google Scholar 

  51. McGuckin CP, Jurga M, Miller AM, Sarnowska A, Wiedner M, Boyle NT, Lynch MA, Jablonska A, Drela K, Lukomska B, Domanska-Janik K, Kenner L, Moriggl R, Degoul O, Perruisseau-Carrier C, Forraz N. Ischemic brain injury: a consortium analysis of key factors involved in mesenchymal stem cell-mediated inflammatory reduction. Arch Biochem Biophys. 2013 Jun;534(1-2):88–97.

    Google Scholar 

  52. Wu X, Wang K, Cui L, et al. Effects of granulocyte-colony stimulating factor on the repair of balloon-injured arteries. Pathology. 2008;40(5):513–9.

    Article  CAS  PubMed  Google Scholar 

  53. Pendharkar AV, Chua JY, Andres RH, Wang N, Gaeta X, Wang H, De A, Choi R, Chen S, Rutt BK, Gambhir SS, Guzman R. Biodistribution of neural stem cells after intravascular therapy for hypoxic-ischemia. Stroke. 2010 Sep;41(9):2064–70.

    Article  PubMed  Google Scholar 

  54. Sinden JD, Muir KW. Stem cells in stroke treatment: the promise and the challenges. Int J Stroke. 2012;7:426–34.

    Article  PubMed  Google Scholar 

  55. Yang M, Wei X, Li J, et al. Changes in host blood factors and brain glia accompanying the functional recovery after systemic administration of bone marrow stem cells in ischemic stroke rats. Cell Transplant. 2010;19:1073–84.

    Article  PubMed  Google Scholar 

  56. Mitkari B, Nitzsche F, Kerkelä E, Kuptsova K, Huttunen J, Nystedt J, Korhonen M, Jolkkonen J. Human bone marrow mesenchymal stem/stromal cells produce efficient localization in the brain and enhanced angiogenesis after intra-arterial delivery in rats with cerebral ischemia, but this is not translated to behavioral recovery. Behav Brain Res. 2014;259:50–9.

    Article  PubMed  Google Scholar 

  57. Vasconcelos-dos-Santos A, Rosado-de-Castro PH, Lopes deSSA, da Costa SJ, Ramos AB, Rodriguez deFG, Barbosa daFLM, Gutfilen B, Mendez-Otero R. Intravenous and intra-arterial administration of bone marrow mononuclear cells after focal cerebral ischemia: Is there a difference in biodistribution and efficacy? Stem Cell Res. 2012 Jul;9(1):1–8. doi: 10.1016/j. scr.2012.02.002.

    Google Scholar 

  58. Yang B, Migliati E, Parsha K, Schaar K, Xi X, Aronowski J, Savitz SI. Intra-arterial delivery is not superior to intravenous delivery of autologous bone marrow mononuclear cells in acute ischemic stroke. Stroke. 2013 Dec;44(12):3463–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Zhang L, Li Y, Romanko M, Kramer BC, Gosiewska A, Chopp M, Hong K. Different routes of administration of human umbilical tissue-derived cells improve functional recovery in the rat after focal cerebral ischemia. Brain Res 2012; 1489:104–2.

    Google Scholar 

  60. Byun JS, Kwak BK, Kim JK, Jung J, Ha BC, Park S. Engraftment of human mesenchymal stem cells in a rat photothrombotic cerebral infarction model : comparison of intra-arterial and intravenous infusion using MRI and histological analysis. J Korean Neurosurg Soc. 2013;54(6):467–76.

    Google Scholar 

  61. Lundberg J, Sodersten E, Sundstrom E, et al. Targeted intra-arterial trans- plantation of stem cells to the injured CNS is more effective than intravenous administration: engraftment is dependent on cell type and adhesion molecule expression. Cell Transplant. 2012;21:333–43.

    Google Scholar 

  62. Fischer UM, Harting MT, Jimenez F, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: The pulmonary first-pass effect. Stem Cells Dev. 2009;18:683–92.

    Google Scholar 

  63. Chua JY, Pendharkar AV, Wang N, et al. Intra-arterial injection of neural stem cells using a microneedle tech- nique does not cause microembolic strokes. J Cereb Blood Flow Metab. 2011;31:1263–71.

    Google Scholar 

  64. Lee JS, et al. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells. 2010;28:1099–106.

    Article  PubMed  Google Scholar 

  65. Li L, Jiang Q, Ding G, Zhang L, Zhang ZG, Li Q, Panda S, Lu M, Ewing JR, Chopp M. Effects of administration route on migration and distribution of neural progenitor cells transplanted into rats with focal cerebral ischemia, an MRI study. J Cereb Blood Flow Metab. 2010;30:653–62.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Walczak P, Zhang J, Gilad AA, et al. Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke. 2008;39:1569–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Misra V, Lal A, El Khoury R, Chen PR, Savitz SI. Intra-arterial delivery of cell therapies for stroke. Stem Cells Dev. 2012;21(7):1007–15.

    Google Scholar 

  68. Kondziolka D, Wechsler L, Goldstein S, Meltzer C, Thulborn KR, Gebel J, Jannetta P, DeCesare S, Elder EM, McGrogan M, Reitman MA, Bynum L. Transplantation of cultured human neuronal cells for patients with stroke. Neurology. 2000;55(4):565–9.

    Article  CAS  PubMed  Google Scholar 

  69. Meltzer CC, Kondziolka D, Villemagne VL, Wechsler L, Goldstein S, Thulborn KR, Gebel J, Elder EM, DeCesare S, Jacobs A. Serial [18F] fluorodeoxyglucose positron emission tomography after human neuronal implantation for stroke. Neurosurgery. 2001;49:586–91. (discussion 591–582).

    Google Scholar 

  70. Nelson PT, Kondziolka D, Wechsler L, et al. Clonal human (hNT) neuron grafts for stroke therapy: neuropathology in a patient 27 months after implantation. Am J Pathol. 2002;160:1201–6.

    Article  PubMed Central  PubMed  Google Scholar 

  71. Kondziolka D, Steinberg GK, Wechsler L, et al. Neu- rotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg. 2005;103:38–45.

    Article  PubMed  Google Scholar 

  72. Jiang Q, Zhang ZG, Ding GL, et al. Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI. Neuroimage. 2005;28:698–707.

    Article  PubMed  Google Scholar 

  73. Modo M, Stroemer RP, Tang E, Patel S, Hodges H. Effects of implantation site of stem cell grafts on behavioral recovery from stroke damage. Stroke. 2002;33:2270–8.

    Article  PubMed  Google Scholar 

  74. Savitz SI, Dinsmore J, Wu J, Henderson GV, Stieg P, Ca- plan LR. Neurotransplantation of fetal porcine cells in patients with basal ganglia infarcts: a preliminary safety and feasibility study. Cerebrovasc Dis. 2005;20:101–7.

    Article  PubMed  Google Scholar 

  75. Rabinovich SS, Seledtsov VI, Banul NV, et al. Cell therapy of brain stroke. Bull Exp Biol Med. 2005;139:126–8.

    Article  CAS  PubMed  Google Scholar 

  76. Bang OY, et al. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol. 2005;57:874–2

    Google Scholar 

  77. Hess DC, Sila CA, Furlan AJ, Wechsler LR, Switzer JA, Mays RW. A double-blind placebo-controlled clinical evaluation of multistem for the treatment of ischemic stroke. Int J Stroke. 2014 April;9:381–386.

    Article  PubMed  Google Scholar 

  78. Banerjee S, Williamson DA, Habib N, Chataway J. The potential benefit of stem cell therapy after stroke: an update. Vasc Health Risk Manag. 2012;8:569–80.

    Google Scholar 

  79. Rosado-de-Castro PH, Pimentel-Coelho PM, da Fonseca LM, de Freitas GR, Mendez-Otero R. The rise of cell therapy trials for stroke: review of published and registered studies. Stem Cells Dev. 2013b;22(15):2095–111.

    Article  PubMed Central  PubMed  Google Scholar 

  80. Mendonca ML, Freitas GR, Silva SA, et al. Safety of intra-arterial autologous bone marrow mononuclear cell trans- plantation for acute ischemic stroke. Arq Bras Cardiol. 2006;86:52–5.

    Google Scholar 

  81. Correa PL, Mesquita CT, Felix RM, Azevedo JC, Barbirato GB, Falcão CH, Gonzalez C, Mendonça ML, Manfrim A, de Freitas G, Oliveira CC, Silva D, Avila D, Borojevic R, Alves S, Oliveira AC Jr, Dohmann HF. Assessment of intra-arterial injected autologous bone marrow mononuclear cell distribution by radioactive labeling in acute ischemic stroke. Clin Nucl Med. 2007 Nov;32(11):839–41.

    Google Scholar 

  82. Kraitchman DL, Tatsumi M, Gilson WD, Ishimori T, Kedziorek D, Walczak P, Segars WP, Chen HH, Fritzges D, Izbudak I, Young RG, Marcelino M, Pittenger MF, Solaiyappan M, Boston RC, Tsui BM, Wahl RL, Bulte JW. Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation. 2005;112(10):1451–61.

    Google Scholar 

  83. Hauger O, Frost EE, van Heeswijk R, et al. MR evaluation of the glomerular homing of magnetically labeled mesenchymal stem cells in a rat model of nephropathy. Radiology 2006;238:200–10.

    Article  PubMed  Google Scholar 

  84. Battistella V, de Freitas GR, da Fonseca LM, Mercante D, Gutfilen B, Goldenberg RC, Dias JV, Kasai-Brunswick TH, Wajnberg E, Rosado-de-Castro PH, Alves-Leon SV, Mendez-Otero R, Andre C. Safety of autologous bone marrow mononuclear cell transplantation in patients with nonacute ischemic stroke. Regen Med. 2011 Jan;6(1):45–52. doi:10.2217/rme.10.97.

    Google Scholar 

  85. Friedrich MA, Martins MP, Araújo MD, Klamt C, Vedolin L, Garicochea B, Raupp EF, Sartori EAmmarJ, Machado DC, Costa JC, Nogueira RG, Rosado-de-Castro PH, Mendez-Otero R, Freitas GR. Intra-arterial infusion of autologous bone marrow mononuclear cells in patients with moderate to severe middle cerebral artery acute ischemic stroke. Cell Transplant. 2012;21(Suppl 1):S13–21. doi:10.3727/096368912X612512.

    Google Scholar 

  86. Jiang Y, Zhu W, Zhu J, Wu L, Xu G, Liu X. Feasibility of delivering mesenchymal stem cells via catheter to the proximal end of the lesion artery in patients with stroke in the territory of the middle cerebral artery. Cell Transplant. 2013;22(12):2291–8.

    Article  PubMed  Google Scholar 

  87. Banerjee S, Bentley P, Hamady M, Marley S, Davis J, et al. Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke. Stem Cells Trans Med. 2014;3:1–9.

    Google Scholar 

  88. Moniche F, Montaner J, Gonzalez-Marcos JR, Carmona M, Piñero P, Espigado I, Cayuela A, Escudero I, de la Torre-LavianaFJ, Boada C, Rosell A, Mayol A, Jimenez MD, Gil-Peralta A, Gonzalez A. Intra-arterial bone marrow mononuclear cell (BM-MNC) transplantation correlates with GM-CSF, PDGF-BB and MMP-2 serum levels in stroke patients: Results from a clinical trial. Cell Transplant. 2014;23:57–64.

    Article  Google Scholar 

  89. Barbosa da Fonseca LM, Battistella V, de Freitas GR, Gutfilen B, Dos Santos Goldenberg RC, Maiolino A, Wajnberg E, Rosado de Castro PH, Mendez-Otero R, Andre C. Early tissue distribution of bone marrow mononuclear cells after intra-arterial delivery in a patient with chronic stroke. Circulation. 2009;120(6):539–41. doi:10.1161/CIRCULATIONAHA.109.863084.

    Google Scholar 

  90. Moniche F, Gonzalez A, Gonzalez-Marcos JR, et al. Intra-arterial bone marrow & mononuclear cells in ischemic stroke: a pilot clinical trial. Stroke. 2012;43:2242–4.

    Article  PubMed  Google Scholar 

  91. Cytomedix Announces Results of RECOVER-Stroke Phase 2 Study (May 5, 2014). http://www.irdirect.net/pr/release/id/607621. Accessed 17 Nov 2014.

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Authors and Affiliations

  1. Neurology, Neurological Institute, University Hospitals Case Medical Center, 11100 Euclid Ave, Bolwell 5120, 44106, Cleveland, OH, USA

    Vikram Jadhav MD

  2. Department of Neurology, Leonard M. Miller School of Medicine, TSL, Lab-230, 1420 NW 9th Avenue, 33136, Miami, FL, USA

    Pallab Bhattacharya PhD

  3. Neurology and Neurosurgery, University of Miami & Jackson Memorial Hospitals, 1120 NW 14th Street, 33136, Miami, FL, USA

    Dileep R. Yavagal MD, FSVIN

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  1. Vikram Jadhav MD
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  2. Pallab Bhattacharya PhD
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  3. Dileep R. Yavagal MD, FSVIN
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Correspondence to Dileep R. Yavagal MD, FSVIN .

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  1. Department of Neurology, Georgia Regents University, Augusta, Georgia, USA

    David C. Hess

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Jadhav, V., Bhattacharya, P., Yavagal, D. (2015). Intra-arterial Approaches to Stem Cell Therapy for Ischemic Stroke. In: Hess, D. (eds) Cell Therapy for Brain Injury. Springer, Cham. https://doi.org/10.1007/978-3-319-15063-5_6

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