Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014 (2014), Article ID 468748, 17 pages
http://dx.doi.org/10.1155/2014/468748
Review Article

Stem Cell-Based Therapies for Ischemic Stroke

1Department of Neurology, No.324 Hospital of PLA, Chongqing 400020, China
2Department of Chemical Defense and Toxicology, Institute of Toxicology, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China

Received 5 December 2013; Accepted 16 January 2014; Published 26 February 2014

Academic Editor: Antonio Salgado

Copyright © 2014 Lei Hao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. R. Marler, “Tissue plasminogen activator for acute ischemic stroke,” New England Journal of Medicine, vol. 333, no. 24, pp. 1581–1587, 1995. View at Publisher · View at Google Scholar · View at Scopus
  2. P. Sandercock, E. Berge, M. Dennis et al., “Cost-effectiveness of thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke assessed by a model based on UK NHS costs,” Stroke, vol. 35, no. 6, pp. 1490–1497, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Thomalla, J. Sobesky, M. Köhrmann et al., “Two tales: hemorrhagic transformation but not parenchymal hemorrhage after thrombolysis is related to severity and duration of ischemia—MRI study of acute stroke patients treated with intravenous tissue plasminogen activator within 6 hours,” Stroke, vol. 38, no. 2, pp. 313–318, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. U. Dirnagl, C. Iadecola, and M. A. Moskowitz, “Pathobiology of ischaemic stroke: an integrated view,” Trends in Neurosciences, vol. 22, no. 9, pp. 391–397, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. E. H. Lo, T. Dalkara, and M. A. Moskowitz, “Mechanisms, challenges and opportunities in stroke,” Nature Reviews Neuroscience, vol. 4, no. 5, pp. 399–415, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. B. Z. Barkho and X. Zhao, “Adult neural stem cells: response to stroke injury and potential for therapeutic applications,” Current Stem Cell Research and Therapy, vol. 6, no. 4, pp. 327–338, 2011. View at Google Scholar · View at Scopus
  7. A. Arvidsson, T. Collin, D. Kirik, Z. Kokaia, and O. Lindvall, “Neuronal replacement from endogenous precursors in the adult brain after stroke,” Nature Medicine, vol. 8, no. 9, pp. 963–970, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. G. Bain, D. Kitchens, M. Yao, J. E. Huettner, and D. I. Gottlieb, “Embryonic stem cells express neuronal properties in vitro,” Developmental Biology, vol. 168, no. 2, pp. 342–357, 1995. View at Publisher · View at Google Scholar · View at Scopus
  9. S. Okabe, K. Forsberg-Nilsson, A. C. Spiro, M. Segal, and R. D. G. McKay, “Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro,” Mechanisms of Development, vol. 59, no. 1, pp. 89–102, 1996. View at Publisher · View at Google Scholar · View at Scopus
  10. B. E. Reubinoff, P. Itsykson, T. Turetsky et al., “Neural progenitors from human embryonic stem cells,” Nature Biotechnology, vol. 19, no. 12, pp. 1134–1140, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. S.-C. Zhang, M. Wernig, I. D. Duncan, O. Brüstle, and J. A. Thomson, “In vitro differentiation of transplantable neural precursors from human embryonic stem cells,” Nature Biotechnology, vol. 19, no. 12, pp. 1129–1133, 2001. View at Publisher · View at Google Scholar · View at Scopus
  12. Q.-L. Ying, M. Stavridis, D. Griffiths, M. Li, and A. Smith, “Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture,” Nature Biotechnology, vol. 21, no. 2, pp. 183–186, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. L. Wei, L. Cui, B. J. Snider et al., “Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia,” Neurobiology of Disease, vol. 19, no. 1-2, pp. 183–193, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. D. Yanagisawa, M. Qi, D.-H. Kim et al., “Improvement of focal ischemia-induced rat dopaminergic dysfunction by striatal transplantation of mouse embryonic stem cells,” Neuroscience Letters, vol. 407, no. 1, pp. 74–79, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Tae-Hoon and L. Yoon-Seok, “Transplantation of mouse embryonic stem cell after middle cerebral artery occlusion,” Acta Cirúrgica Brasileira, vol. 27, no. 4, pp. 333–339.
  16. D. Solter, “From teratocarcinomas to embryonic stem cells and beyond: a history of embryonic stem cell research,” Nature Reviews Genetics, vol. 7, no. 4, pp. 319–327, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. B. E. Reubinoff, M. F. Pera, C.-Y. Fong, A. Trounson, and A. Bongso, “Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro,” Nature Biotechnology, vol. 18, no. 4, pp. 399–404, 2000. View at Google Scholar
  18. J. A. Thomson, “Embryonic stem cell lines derived from human blastocysts,” Science, vol. 282, no. 5391, pp. 1145–1147, 1998. View at Google Scholar · View at Scopus
  19. M. M. Daadi, A.-L. Maag, and G. K. Steinberg, “Adherent self-renewable human embryonic stem cell-derived neural stem cell line: functional engraftment in experiment stroke model,” PLoS ONE, vol. 3, no. 2, Article ID e1644, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. D.-Y. Kim, S.-H. Park, S.-U. Lee et al., “Effect of human embryonic stem cell-derived neuronal precursor cell transplantation into the cerebral infarct model of rat with exercise,” Neuroscience Research, vol. 58, no. 2, pp. 164–175, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. A. U. Hicks, R. S. Lappalainen, S. Narkilahti et al., “Transplantation of human embryonic stem cell-derived neural precursor cells and enriched environment after cortical stroke in rats: cell survival and functional recovery,” European Journal of Neuroscience, vol. 29, no. 3, pp. 562–574, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. C. Bühnemann, A. Scholz, C. Bernreuther et al., “Neuronal differentiation of transplanted embryonic stem cell-derived precursors in stroke lesions of adult rats,” Brain, vol. 129, no. 12, pp. 3238–3248, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. J. Hayashi, Y. Takagi, H. Fukuda et al., “Primate embryonic stem cell-derived neuronal progenitors transplanted into ischemic brain,” Journal of Cerebral Blood Flow and Metabolism, vol. 26, no. 7, pp. 906–914, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. K.-C. Sonntag, J. Pruszak, T. Yoshizaki, J. Van Arensbergen, R. Sanchez-Pernaute, and O. Isacson, “Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin,” Stem Cells, vol. 25, no. 2, pp. 411–418, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Brederlau, A. S. Correia, S. V. Anisimov et al., “Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: effect of in vitro differentiation on graft survival and teratoma formation,” Stem Cells, vol. 24, no. 6, pp. 1433–1440, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. C. Seminatore, J. Polentes, D. Ellman et al., “The postischemic environment differentially impacts teratoma or tumor formation after transplantation of human embryonic stem cell-derived neural progenitors,” Stroke, vol. 41, no. 1, pp. 153–159, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. N. Oyamada, H. Itoh, M. Sone et al., “Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice,” Journal of Translational Medicine, vol. 6, article 54, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Takahashi and S. Yamanaka, “Induction of pluripotent stem Cells from mouse embryonic and adult fibroblast cultures by defined factors,” Cell, vol. 126, no. 4, pp. 663–676, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. J. Cai, W. Li, H. Su et al., “Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells,” Journal of Biological Chemistry, vol. 285, no. 15, pp. 11227–11234, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. P. A. Tat, H. Sumer, K. L. Jones, K. Upton, and P. J. Verma, “The efficient generation of induced pluripotent stem (iPS) cells from adult mouse adipose tissue-derived and neural stem cells,” Cell Transplantation, vol. 19, no. 5, pp. 525–536, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. S.-J. Chen, C.-M. Chang, S.-K. Tsai et al., “Functional improvement of focal cerebral ischemia injury by subdural transplantation of induced pluripotent stem cells with fibrin glue,” Stem Cells and Development, vol. 19, no. 11, pp. 1757–1767, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Jiang, L. Lv, H. Ji et al., “Induction of pluripotent stem cells transplantation therapy for ischemic stroke,” Molecular and Cellular Biochemistry, vol. 354, no. 1-2, pp. 67–75, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Kawai, T. Yamashita, Y. Ohta et al., “Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain,” Journal of Cerebral Blood Flow and Metabolism, vol. 30, no. 8, pp. 1487–1493, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Zhao, Z.-N. Zhang, Z. Rong, and Y. Xu, “Immunogenicity of induced pluripotent stem cells,” Nature, vol. 474, no. 7350, pp. 212–216, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. T. Yamashita, H. Kawai, F. Tian, Y. Ohta, and K. Abe, “Tumorigenic development of induced pluripotent stem cells in ischemic mouse brain,” Cell Transplantation, vol. 20, no. 6, pp. 883–891, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. G.-L. Ming and H. Song, “Adult neurogenesis in the mammalian brain: significant answers and significant questions,” Neuron, vol. 70, no. 4, pp. 687–702, 2011. View at Publisher · View at Google Scholar · View at Scopus
  37. P. Thored, A. Arvidsson, E. Cacci et al., “Persistent production of neurons from adult brain stem cells during recovery after stroke,” Stem Cells, vol. 24, no. 3, pp. 739–747, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. J. S. Kim, “Cytokines and adhesion molecules in stroke and related diseases,” Journal of the Neurological Sciences, vol. 137, no. 2, pp. 69–78, 1996. View at Publisher · View at Google Scholar · View at Scopus
  39. Z. G. Zhang, L. Zhang, W. Tsang et al., “Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia,” Journal of Cerebral Blood Flow and Metabolism, vol. 22, no. 4, pp. 379–392, 2002. View at Google Scholar · View at Scopus
  40. V. I. Otto, S. M. Gloor, S. Frentzel et al., “The production of macrophage inflammatory protein-2 induced by soluble intercellular adhesion molecule-1 in mouse astrocytes is mediated by src tyrosine kinases and p42/44 mitogen-activated protein kinase,” Journal of Neurochemistry, vol. 80, no. 5, pp. 824–834, 2002. View at Publisher · View at Google Scholar · View at Scopus
  41. A. F. Hallbergson, C. Gnatenco, and D. A. Peterson, “Neurogenesis and brain injury: managing a renewable resource for repair,” Journal of Clinical Investigation, vol. 112, no. 8, pp. 1128–1133, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. X. Wang, X. Mao, L. Xie, D. A. Greenberg, and K. Jin, “Involvement of Notch1 signaling in neurogenesis in the subventricular zone of normal and ischemic rat brain in vivo,” Journal of Cerebral Blood Flow and Metabolism, vol. 29, no. 10, pp. 1644–1654, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. J. Chou, B. K. Harvey, C.-F. Chang, H. Shen, M. Morales, and Y. Wang, “Neuroregenerative effects of BMP7 after stroke in rats,” Journal of the Neurological Sciences, vol. 240, no. 1-2, pp. 21–29, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. J. M. Plane, J. T. Whitney, T. Schallert, and J. M. Parent, “Retinoic acid and environmental enrichment alter subventricular zone and striatal neurogenesis after stroke,” Experimental Neurology, vol. 214, no. 1, pp. 125–134, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. J. R. Sims, S.-W. Lee, K. Topalkara et al., “Sonic hedgehog regulates ischemia/hypoxia-induced neural progenitor proliferation,” Stroke, vol. 40, no. 11, pp. 3618–3626, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. R. E. Iosif, H. Ahlenius, C. T. Ekdahl et al., “Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1,” Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 9, pp. 1574–1587, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. R. Guzman, A. de los Angeles, S. Cheshier et al., “Intracarotid injection of fluorescence activated cell-sorted CD49d-positive neural stem cells improves targeted cell delivery and behavior after stroke in a mouse stroke model,” Stroke, vol. 39, no. 4, pp. 1300–1306, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. F. I. Staquicini, E. Dias-Neto, J. Li et al., “Discovery of a functional protein complex of netrin-4, laminin γ1 chain, and integrin α6β1 in mouse neural stem cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2903–2908, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Benraiss, E. Chmielnicki, K. Lerner, D. Roh, and S. A. Goldman, “Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain,” Journal of Neuroscience, vol. 21, no. 17, pp. 6718–6731, 2001. View at Google Scholar · View at Scopus
  50. K. Jin, Y. Zhu, Y. Sun, X. O. Mao, L. Xie, and D. A. Greenberg, “Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 18, pp. 11946–11950, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. L. Wang, Z. Zhang, Y. Wang, R. Zhang, and M. Chopp, “Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats,” Stroke, vol. 35, no. 7, pp. 1732–1737, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. A. Kimura, T. Ohmori, Y. Kashiwakura et al., “Antagonism of sphingosine 1-phosphate receptor-2 enhances migration of neural progenitor cells toward an area of brain infarction,” Stroke, vol. 39, no. 12, pp. 3411–3417, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. M. A. Rueger, S. Muesken, M. Walberer et al., “Effects of minocycline on endogenous neural stem cells after experimental stroke,” Neuroscience, vol. 215, pp. 174–183, 2012. View at Google Scholar
  54. H. Ehrenreich, K. Weissenborn, H. Prange et al., “Recombinant human erythropoietin in the treatment of acute ischemic stroke,” Stroke, vol. 40, no. 12, pp. e647–e656, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. T. Garzón-Muvdi and A. Quiñones-Hinojosa, “Neural stem cell niches and homing: recruitment and integration into functional tissues,” ILAR Journal, vol. 51, no. 1, pp. 3–23, 2010. View at Google Scholar · View at Scopus
  56. O. Lindvall and Z. Kokaia, “Stem cell research in stroke: how far from the clinic?” Stroke, vol. 42, no. 8, pp. 2369–2375, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. J. Hori, T. F. Ng, M. Shatos, H. Klassen, J. W. Streilein, and M. J. Young, “Neural progenitor cells lack immunogenicity and resist destruction as allografts,” Stem Cells, vol. 21, no. 4, pp. 405–416, 2003. View at Google Scholar · View at Scopus
  58. L. Yin, S.-L. Fu, G.-Y. Shi et al., “Expression and regulation of major histocompatibility complex on neural stem cells and their lineages,” Stem Cells and Development, vol. 17, no. 1, pp. 53–65, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. R. Laguna Goya, R. Busch, R. Mathur, A. J. Coles, and R. A. Barker, “Human fetal neural precursor cells can up-regulate MHC class I and class II expression and elicit CD4 and CD8 T cell proliferation,” Neurobiology of Disease, vol. 41, no. 2, pp. 407–414, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Jablonska, M. Janowski, and B. Lukomska, “Different methods of immunosuppresion do not prolong the survival of human cord blood-derived neural stem cells transplanted into focal brain-injured immunocompetent rats,” Acta Neurobiologiae Experimentalis, vol. 73, no. 1, pp. 88–101, 2013. View at Google Scholar
  61. K. Takahashi, T. Yasuhara, T. Shingo et al., “Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells,” Brain Research, vol. 1234, pp. 172–182, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. M. B. Jensen, H. Yan, R. Krishnaney-Davison, A. Al Sawaf, and S. C. Zhang, “Survival and differentiation of transplanted neural stem cells derived from human induced pluripotent stem cells in a rat stroke model,” Journal of Stroke and Cerebrovascular Diseases, vol. 22, no. 4, p. 304.
  63. W. Zhu, Y. Mao, Y. Zhao et al., “Transplantation of vascular endothelial growth factor-transfected neural stem cells into the rat brain provides neuroprotection after transient focal cerebral ischemia,” Neurosurgery, vol. 57, no. 2, pp. 325–332, 2005. View at Publisher · View at Google Scholar · View at Scopus
  64. Z.-H. Zhang, R.-Z. Wang, R.-Z. Wang et al., “Transplantation of neural stem cells modified by human neurotrophin-3 promotes functional recovery after transient focal cerebral ischemia in rats,” Neuroscience Letters, vol. 444, no. 3, pp. 227–230, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. B. Jenny, M. Kanemitsu, O. Tsupykov et al., “Fibroblast growth factor-2 overexpression in transplanted neural progenitors promotes perivascular cluster formation with a neurogenic potential,” Stem Cells, vol. 27, no. 6, pp. 1309–1317, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. B. Chen, X.-Q. Gao, C.-X. Yang et al., “Neuroprotective effect of grafting GDNF gene-modified neural stem cells on cerebral ischemia in rats,” Brain Research, vol. 1284, pp. 1–11, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. H. J. Lee, I. J. Lim, M. C. Lee, and S. U. Kim, “Human neural stem cells genetically modified to overexpress brain-derived neurotrophic factor promote functional recovery and neuroprotection in a mouse stroke model,” Journal of Neuroscience Research, vol. 88, no. 15, pp. 3282–3294, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. W. Wu, X. Chen, C. Hu, J. Li, Z. Yu, and W. Cai, “Transplantation of neural stem cells expressing hypoxia-inducible factor-1α (HIF-1α) improves behavioral recovery in a rat stroke model,” Journal of Clinical Neuroscience, vol. 17, no. 1, pp. 92–95, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Kelly, T. M. Bliss, A. K. Shah et al., “Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 32, pp. 11839–11844, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. K. Chu, M. Kim, K.-I. Park et al., “Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia,” Brain Research, vol. 1016, no. 2, pp. 145–153, 2004. View at Publisher · View at Google Scholar · View at Scopus
  71. K. Chu, K.-I. Park, S.-T. Lee et al., “Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia,” Neuroscience Research, vol. 53, no. 4, pp. 384–390, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. P. Zhang, J. Li, Y. Liu et al., “Human neural stem cell transplantation attenuates apoptosis and improves neurological functions after cerebral ischemia in rats,” Acta Anaesthesiologica Scandinavica, vol. 53, no. 9, pp. 1184–1191, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. P. Stroemer, S. Patel, A. Hope, C. Oliveira, K. Pollock, and J. Sinden, “The neural stem cell line CTX0E03 promotes behavioral recovery and endogenous neurogenesis after experimental stroke in a dose-dependent fashion,” Neurorehabilitation and Neural Repair, vol. 23, no. 9, pp. 895–908, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Jin, X. Mao, L. Xie et al., “Transplantation of human neural precursor cells in Matrigel scaffolding improves outcome from focal cerebral ischemia after delayed postischemic treatment in rats,” Journal of Cerebral Blood Flow and Metabolism, vol. 30, no. 3, pp. 534–544, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. J. Minnerup, J. B. Kim, A. Schmidt et al., “Effects of neural progenitor cells on sensorimotor recovery and endogenous repair mechanisms after photothrombotic stroke,” Stroke, vol. 42, no. 6, pp. 1757–1763, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. C. Sun, H. Zhang, J. Li et al., “Modulation of the major histocompatibility complex by neural stem cell-derived neurotrophic factors used for regenerative therapy in a rat model of stroke,” Journal of Translational Medicine, vol. 8, article 77, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Bacigaluppi, S. Pluchino, L. P. Jametti et al., “Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms,” Brain, vol. 132, no. 8, pp. 2239–2251, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. S.-W. Jeong, K. Chu, K.-H. Jung, S. U. Kim, M. Kim, and J.-K. Roh, “Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage,” Stroke, vol. 34, no. 9, pp. 2258–2263, 2003. View at Publisher · View at Google Scholar · View at Scopus
  79. H. Yu, B. Cao, M. Feng et al., “Combinated transplantation of neural stem cells and collagen type I promote functional recovery after cerebral ischemia in rats,” Anatomical Record, vol. 293, no. 5, pp. 911–917, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. P. Zhang, J. Li, Y. Liu et al., “Human embryonic neural stem cell transplantation increases subventricular zone cell proliferation and promotes peri-infarct angiogenesis after focal cerebral ischemia,” Neuropathology, vol. 31, no. 4, pp. 384–391, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. M. Gaudier, B. S. Schuwirth, S. L. Westcott, and D. B. Wigley, “Structural basis of DNA replication origin recognition by an ORC protein,” Science, vol. 317, no. 5842, pp. 1213–1216, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. J. Imitola, K. Raddassi, K. I. Park et al., “Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1α/CXC chemokine receptor 4 pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 52, pp. 18117–18122, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. F.-J. Mueller, N. Serobyan, I. U. Schraufstatter et al., “Adhesive interactions between human neural stem cells and inflamed human vascular endothelium are mediated by integrins,” Stem Cells, vol. 24, no. 11, pp. 2367–2372, 2006. View at Publisher · View at Google Scholar · View at Scopus
  84. J. J. Ohab, S. Fleming, A. Blesch, and S. T. Carmichael, “A neurovascular niche for neurogenesis after stroke,” Journal of Neuroscience, vol. 26, no. 50, pp. 13007–13016, 2006. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Pluchino, A. Quattrini, E. Brambilla et al., “Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis,” Nature, vol. 422, no. 6933, pp. 688–694, 2003. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Pluchino, L. Zanotti, B. Rossi et al., “Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism,” Nature, vol. 436, no. 7048, pp. 266–271, 2005. View at Publisher · View at Google Scholar · View at Scopus
  87. K. Sawamoto, H. Wichterle, O. Gonzalez-Perez et al., “New neurons follow the flow of cerebrospinal fluid in the adult brain,” Science, vol. 311, no. 5761, pp. 629–632, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. R. H. Andres, R. Choi, A. V. Pendharkar et al., “The CCR2/CCL2 interaction mediates the transendothelial recruitment of intravascularly delivered neural stem cells to the ischemic brain,” Stroke, vol. 42, no. 10, pp. 2923–2931, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. T. R. Doeppner, T. A. Ewert, L. Tonges et al., “Transduction of neural precursor cells with TAT-heat shock protein 70 chaperone: therapeutic potential against ischemic stroke after intrastriatal and systemic transplantation,” Stem Cells, vol. 30, no. 6, pp. 1297–1310, 2012. View at Google Scholar
  90. V. Darsalia, S. J. Allison, C. Cusulin et al., “Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain,” Journal of Cerebral Blood Flow and Metabolism, vol. 31, no. 1, pp. 235–242, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. D.-E. Kim, D. Schellingerhout, K. Ishii, K. Shah, and R. Weissleder, “Imaging of stem cell recruitment to ischemic infarcts in a murine model,” Stroke, vol. 35, no. 4, pp. 952–957, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. R. Guzman, T. Bliss, A. De Los Angeles, M. Moseley, T. Palmer, and G. Steinberg, “Neural progenitor cells transplanted into the uninjured brain undergo targeted migration after stroke onset,” Journal of Neuroscience Research, vol. 86, no. 4, pp. 873–882, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. P. Riess, C. Zhang, K. E. Saatman et al., “Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury,” Neurosurgery, vol. 51, no. 4, pp. 1043–1054, 2002. View at Publisher · View at Google Scholar · View at Scopus
  94. J. M. Zhu, Y. Y. Zhao, S. D. Chen, W. H. Zhang, L. Lou, and X. Jin, “Functional recovery after transplantation of neural stem cells modified by brain-derived neurotrophic factor in rats with cerebral ischaemia,” Journal of International Medical Research, vol. 39, no. 2, pp. 488–498, 2011. View at Google Scholar · View at Scopus
  95. U. Englund, A. Björklund, K. Wictorin, O. Lindvall, and M. Kokaia, “Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 26, pp. 17089–17094, 2002. View at Publisher · View at Google Scholar · View at Scopus
  96. Z. Nan, A. Grande, C. D. Sanberg, P. R. Sanberg, and W. C. Low, “Infusion of human umbilical cord blood ameliorates neurologic deficits in rats with hemorrhagic brain injury,” Annals of the New York Academy of Sciences, vol. 1049, pp. 84–96, 2005. View at Publisher · View at Google Scholar · View at Scopus
  97. B. Schaller, R. H. Andres, A. W. Huber et al., “Effect of GDNF on differentiation of cultured ventral mesencephalic dopaminergic and non-dopaminergic calretinin-expressing neurons,” Brain Research, vol. 1036, no. 1-2, pp. 163–172, 2005. View at Publisher · View at Google Scholar · View at Scopus
  98. K. M. Harms, L. Li, and L. A. Cunningham, “Murine neural stem/progenitor cells protect neurons against ischemia by HIF-1alpha-regulated VEGF signaling,” PLoS ONE, vol. 5, no. 3, Article ID e9767, 2010. View at Google Scholar · View at Scopus
  99. R. H. Andres, N. Horie, W. Slikker et al., “Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain,” Brain, vol. 134, no. 6, pp. 1777–1789, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. K. Jin, L. Xie, X. Mao et al., “Effect of human neural precursor cell transplantation on endogenous neurogenesis after focal cerebral ischemia in the rat,” Brain Research, vol. 1374, pp. 56–62, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. K. Jin, X. Wang, L. Xie, X. O. Mao, and D. A. Greenberg, “Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 17, pp. 7993–7998, 2010. View at Publisher · View at Google Scholar · View at Scopus
  102. S.-T. Lee, K. Chu, K.-H. Jung et al., “Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke,” Brain, vol. 131, no. 3, pp. 616–629, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. Z. Hassani, J. O'Reilly, Y. Pearse et al., “Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke,” PLoS ONE, vol. 7, no. 11, Article ID e50444, 2012. View at Google Scholar
  104. Q. Jiang, G. Z. Zheng, L. D. Guang et al., “Investigation of neural progenitor cell induced angiogenesis after embolic stroke in rat using MRI,” NeuroImage, vol. 28, no. 3, pp. 698–707, 2005. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Pluchino and G. Martino, “Neural stem cell-mediated immunomodulation: repairing the haemorrhagic brain,” Brain, vol. 131, no. 3, pp. 604–605, 2008. View at Publisher · View at Google Scholar · View at Scopus
  106. A. J. Friedenstein, I. I. Piatetzky-Shapiro, and K. V. Petrakova, “Osteogenesis in transplants of bone marrow cells,” Journal of Embryology and Experimental Morphology, vol. 16, no. 3, pp. 381–390, 1966. View at Google Scholar · View at Scopus
  107. Z. Zou, Y. Zhang, L. Hao et al., “More insight into mesenchymal stem cells and their effects inside the body,” Expert Opinion on Biological Therapy, vol. 10, no. 2, pp. 215–230, 2010. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Dominici, K. Le Blanc, I. Mueller et al., “Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement,” Cytotherapy, vol. 8, no. 4, pp. 315–317, 2006. View at Publisher · View at Google Scholar · View at Scopus
  109. M. F. Pittenger, A. M. Mackay, S. C. Beck et al., “Multilineage potential of adult human mesenchymal stem cells,” Science, vol. 284, no. 5411, pp. 143–147, 1999. View at Publisher · View at Google Scholar · View at Scopus
  110. K. Kurozumi, K. Nakamura, T. Tamiya et al., “BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model,” Molecular Therapy, vol. 9, no. 2, pp. 189–197, 2004. View at Publisher · View at Google Scholar · View at Scopus
  111. H. Liu, O. Honmou, K. Harada et al., “Neuroprotection by PIGF gene-modified human mesenchymal stem cells after cerebral ischaemia,” Brain, vol. 129, no. 10, pp. 2734–2745, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. K. Toyama, O. Honmou, K. Harada et al., “Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia,” Experimental Neurology, vol. 216, no. 1, pp. 47–55, 2009. View at Publisher · View at Google Scholar · View at Scopus
  113. K. Kurozumi, K. Nakamura, T. Tamiya et al., “Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model,” Molecular Therapy, vol. 11, no. 1, pp. 96–104, 2005. View at Publisher · View at Google Scholar · View at Scopus
  114. N. Ikeda, N. Nonoguchi, Z. Z. Ming 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, vol. 36, no. 12, pp. 2725–2730, 2005. View at Publisher · View at Google Scholar · View at Scopus
  115. D.-C. Ding, W.-C. Shyu, M.-F. Chiang et al., “Enhancement of neuroplasticity through upregulation of β1-integrin in human umbilical cord-derived stromal cell implanted stroke model,” Neurobiology of Disease, vol. 27, no. 3, pp. 339–353, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. J. Chen, Y. Li, L. Wang, M. Lu, X. Zhang, and M. Chopp, “Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats,” Journal of the Neurological Sciences, vol. 189, no. 1-2, pp. 49–57, 2001. View at Publisher · View at Google Scholar · View at Scopus
  117. H. Xin, Y. Li, L. H. Shen et al., “Increasing tPa activity in astrocytes induced by multipotent mesenchymal stromal cells facilitate neurite outgrowth after stroke in the mouse,” PLoS ONE, vol. 5, no. 2, Article ID e9027, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. L. H. Shen, H. Xin, Y. Li et al., “Endogenous tissue plasminogen activator mediates bone marrow stromal cell-induced neurite remodeling after stroke in mice,” Stroke, vol. 42, no. 2, pp. 459–464, 2011. View at Publisher · View at Google Scholar · View at Scopus
  119. S. Leu, Y.-C. Lin, C.-M. Yuen et al., “Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats,” Journal of Translational Medicine, vol. 8, article 63, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. Y. Li, J. Chen, X. G. Chen et al., “Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery,” Neurology, vol. 59, no. 4, pp. 514–523, 2002. View at Google Scholar · View at Scopus
  121. T. Honma, O. Honmou, S. Iihoshi et al., “Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat,” Experimental Neurology, vol. 199, no. 1, pp. 56–66, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. T. Onda, O. Honmou, K. Harada, K. Houkin, H. Hamada, and J. D. Kocsis, “Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia,” Journal of Cerebral Blood Flow and Metabolism, vol. 28, no. 2, pp. 329–340, 2008. View at Publisher · View at Google Scholar · View at Scopus
  123. R. Ukai, O. Honmou, K. Harada, K. Houkin, H. Hamada, and J. D. Kocsis, “Mesenchymal stem cells derived from peripheral blood protects against ischemia,” Journal of Neurotrauma, vol. 24, no. 3, pp. 508–520, 2007. View at Publisher · View at Google Scholar · View at Scopus
  124. Y. Omori, O. Honmou, K. Harada, J. Suzuki, K. Houkin, and J. D. Kocsis, “Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats,” Brain Research, vol. 1236, pp. 30–38, 2008. View at Publisher · View at Google Scholar · View at Scopus
  125. X. Bao, M. Feng, J. Wei et al., “Transplantation of Flk-1+ human bone marrow-derived mesenchymal stem cells promotes angiogenesis and neurogenesis after cerebral ischemia in rats,” European Journal of Neuroscience, vol. 34, no. 1, pp. 87–98, 2011. View at Publisher · View at Google Scholar · View at Scopus
  126. Y. Li, J. Chen, L. Wang, M. Lu, and M. Chopp, “Treatment of stroke in rat with intracarotid administration of marrow stromal cells,” Neurology, vol. 56, no. 12, pp. 1666–1672, 2001. View at Google Scholar · View at Scopus
  127. S.-H. Koh, K. S. Kim, M. R. Choi et al., “Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats,” Brain Research, vol. 1229, pp. 233–248, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. J. Li, H. Zhu, Y. Liu et al., “Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macaca fascicularis,” Brain Research, vol. 1334, pp. 65–72, 2010. View at Publisher · View at Google Scholar · View at Scopus
  129. M. Yang, X. Wei, J. Li, L. A. Heine, R. Rosenwasser, and L. Iacovitti, “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 Transplantation, vol. 19, no. 9, pp. 1073–1084, 2010. View at Publisher · View at Google Scholar · View at Scopus
  130. E. Keimpema, M. R. Fokkens, Z. Nagy et al., “Early transient presence of implanted bone marrow stem cells reduces lesion size after cerebral ischaemia in adult rats,” Neuropathology and Applied Neurobiology, vol. 35, no. 1, pp. 89–102, 2009. View at Publisher · View at Google Scholar · View at Scopus
  131. N. Pavlichenko, I. Sokolova, S. Vijde et al., “Mesenchymal stem cells transplantation could be beneficial for treatment of experimental ischemic stroke in rats,” Brain Research, vol. 1233, pp. 203–213, 2008. View at Publisher · View at Google Scholar · View at Scopus
  132. H. Ohtaki, J. H. Ylostalo, J. E. Foraker et al., “Stem/progenitor cells from bone marrow decrease neuronal death in global ischemia by modulation of inflammatory/immune responses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 38, pp. 14638–14643, 2008. View at Publisher · View at Google Scholar · View at Scopus
  133. M.-Z. Zhao, N. Nonoguchi, N. Ikeda et al., “Novel therapeutic strategy for stroke in rats by bone marrow stromal cells and ex vivo HGF gene transfer with HSV-1 vector,” Journal of Cerebral Blood Flow and Metabolism, vol. 26, no. 9, pp. 1176–1188, 2006. View at Publisher · View at Google Scholar · View at Scopus
  134. J. Zhang, Y. Li, J. Chen et al., “Expression of insulin-like growth factor 1 and receptor in ischemic rats treated with human marrow stromal cells,” Brain Research, vol. 1030, no. 1, pp. 19–27, 2004. View at Publisher · View at Google Scholar · View at Scopus
  135. A. Zacharek, A. Shehadah, J. Chen et al., “Comparison of bone marrow stromal cells derived from stroke and normal rats for stroke treatment,” Stroke, vol. 41, no. 3, pp. 524–530, 2010. View at Publisher · View at Google Scholar · View at Scopus
  136. L. Wei, J. L. Fraser, Z.-Y. Lu, X. Hu, and S. P. Yu, “Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats,” Neurobiology of Disease, vol. 46, no. 3, p. 635, 2012. View at Publisher · View at Google Scholar · View at Scopus
  137. K. Wakabayashi, A. Nagai, A. M. Sheikh et al., “Transplantation of human mesenchymal stem cells promotes functional improvement and increased expression of neurotrophic factors in a rat focal cerebral ischemia model,” Journal of Neuroscience Research, vol. 88, no. 5, pp. 1017–1025, 2010. View at Publisher · View at Google Scholar · View at Scopus
  138. L.-K. Tsai, Z. Wang, J. Munasinghe, Y. Leng, P. Leeds, and D.-M. Chuang, “Mesenchymal stem cells primed with valproate and lithium robustly migrate to infarcted regions and facilitate recovery in a stroke model,” Stroke, vol. 42, no. 10, pp. 2932–2939, 2011. View at Publisher · View at Google Scholar · View at Scopus
  139. A. Kranz, D.-C. Wagner, M. Kamprad et al., “Transplantation of placenta-derived mesenchymal stromal cells upon experimental stroke in rats,” Brain Research, vol. 1315, pp. 128–136, 2010. View at Publisher · View at Google Scholar · View at Scopus
  140. M. Gutierrez-Fernandez, B. Rodriguez-Frutos, J. Ramos-Cejudo et al., “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 Research & Therapy, vol. 4, no. 1, article 11, 2013. View at Google Scholar
  141. G. J.-R. Delcroix, P. C. Schiller, J.-P. Benoit, and C. N. Montero-Menei, “Adult cell therapy for brain neuronal damages and the role of tissue engineering,” Biomaterials, vol. 31, no. 8, pp. 2105–2120, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. J. Fiedler, F. Leucht, J. Waltenberger, C. Dehio, and R. E. Brenner, “VEGF-A and PlGF-1 stimulate chemotactic migration of human mesenchymal progenitor cells,” Biochemical and Biophysical Research Communications, vol. 334, no. 2, pp. 561–568, 2005. View at Publisher · View at Google Scholar · View at Scopus
  143. L. Wang, Y. Li, X. Chen et al., “MCP-1, MIP-1, IL-8 and ischemic cerebral tissue enhance human bone marrow stromal cell migration in interface culture,” Hematology, vol. 7, no. 2, pp. 113–117, 2002. View at Google Scholar · View at Scopus
  144. A. Bhasin, M. V. Padma Srivastava, S. Mohanty, R. Bhatia, S. S. Kumaran, and S. Bose, “Stem cell therapy: a clinical trial of stroke,” Clinical Neurology and Neurosurgery, vol. 115, no. 7, pp. 1003–1008, 2013. View at Google Scholar
  145. L. H. Shen, Y. Li, J. Chen et al., “One-year follow-up after bone marrow stromal cell treatment in middle-aged female rats with stroke,” Stroke, vol. 38, no. 7, pp. 2150–2156, 2007. View at Publisher · View at Google Scholar · View at Scopus
  146. E. Mezey, K. J. Chandross, G. Harta, R. A. Maki, and S. R. McKercher, “Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow,” Science, vol. 290, no. 5497, pp. 1779–1782, 2000. View at Publisher · View at Google Scholar · View at Scopus
  147. É. Mezey, S. Key, G. Vogelsang, I. Szalayova, G. David Lange, and B. Crain, “Transplanted bone marrow generates new neurons in human brains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 3, pp. 1364–1369, 2003. View at Publisher · View at Google Scholar · View at Scopus
  148. L.-R. Zhao, W.-M. Duan, M. Reyes, C. D. Keene, C. M. Verfaillie, and W. C. Low, “Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats,” Experimental Neurology, vol. 174, no. 1, pp. 11–20, 2002. View at Publisher · View at Google Scholar · View at Scopus
  149. L. E. Fox, J. Shen, K. Ma et al., “Membrane properties of neuron-like cells generated from adult human bone-marrow-derived mesenchymal stem cells,” Stem Cells and Development, vol. 19, no. 12, pp. 1831–1841, 2010. View at Publisher · View at Google Scholar · View at Scopus
  150. E. Pacary, H. Legros, S. Valable et al., “Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells,” Journal of Cell Science, vol. 119, no. 13, pp. 2667–2678, 2006. View at Publisher · View at Google Scholar · View at Scopus
  151. S. Wislet-Gendebien, G. Hans, P. Leprince, J.-M. Rigo, G. Moonen, and B. Rogister, “Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype,” Stem Cells, vol. 23, no. 3, pp. 392–402, 2005. View at Publisher · View at Google Scholar · View at Scopus
  152. G. Paul, I. Özen, N. S. Christophersen et al., “The adult human brain harbors multipotent perivascular mesenchymal stem cells,” PLoS ONE, vol. 7, no. 4, Article ID e35577, 2012. View at Publisher · View at Google Scholar · View at Scopus
  153. J. Chen, Y. Li, M. Katakowski et al., “Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat,” Journal of Neuroscience Research, vol. 73, no. 6, pp. 778–786, 2003. View at Publisher · View at Google Scholar · View at Scopus
  154. J. Chen, Y. Li, L. Wang, M. Lu, and M. Chopp, “Caspase inhibition by Z-VAD increases the survival of grafted bone marrow cells and improves functional outcome after MCAo in rats,” Journal of the Neurological Sciences, vol. 199, no. 1-2, pp. 17–24, 2002. View at Publisher · View at Google Scholar · View at Scopus
  155. M. Chopp, Y. Li, and J. Zhang, “Plasticity and remodeling of brain,” Journal of the Neurological Sciences, vol. 265, no. 1-2, pp. 97–101, 2008. View at Publisher · View at Google Scholar · View at Scopus
  156. J. Chen, Z. G. Zhang, Y. Li et al., “Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats,” Circulation Research, vol. 92, no. 6, pp. 692–699, 2003. View at Publisher · View at Google Scholar · View at Scopus
  157. J. Chen and M. Chopp, “Neurorestorative treatment of stroke: cell and pharmacological approaches,” NeuroRx, vol. 3, no. 4, pp. 466–473, 2006. View at Publisher · View at Google Scholar · View at Scopus
  158. X. Chen, Y. Li, L. Wang et al., “Ischemic rat brain extracts induce human marrow stromal cell growth factor production,” Neuropathology, vol. 22, no. 4, pp. 275–279, 2002. View at Publisher · View at Google Scholar · View at Scopus
  159. H. Ghasemi, T. Ghazanfari, R. Yaraee et al., “Evaluation of relationship between the serum levels of inflammatory mediators and ocular injuries induced by sulfur mustard: Sardasht-Iran Cohort Study,” International Immunopharmacology, vol. 9, no. 13-14, pp. 1494–1498, 2009. View at Publisher · View at Google Scholar · View at Scopus
  160. F. Guo, S. Lv, Y. Lou et al., “Bone marrow stromal cells enhance the angiogenesis in ischaemic cortex after stroke: involvement of notch signalling,” Cell Biology International, vol. 36, no. 11, pp. 997–1004, 2012. View at Google Scholar
  161. W.-R. Schäbitz, T. Steigleder, C. M. Cooper-Kuhn et al., “Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis,” Stroke, vol. 38, no. 7, pp. 2165–2172, 2007. View at Publisher · View at Google Scholar · View at Scopus
  162. F. Scheibe, J. Ladhoff, J. Huck et al., “Immune effects of mesenchymal stromal cells in experimental stroke,” Journal of Cerebral Blood Flow and Metabolism, vol. 32, no. 8, p. 1578, 2012. View at Publisher · View at Google Scholar · View at Scopus
  163. S. W. Yoo, D. Y. Chang, H. S. Lee et al., “Immune following suppression mesenchymal stem cell transplantation in the ischemic brain is mediated by TGF-beta,” Neurobiology of Disease, vol. 58, pp. 249–257, 2013. View at Google Scholar
  164. O. Honmou, K. Houkin, T. Matsunaga et al., “Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke,” Brain, vol. 134, no. 6, pp. 1790–1807, 2011. View at Publisher · View at Google Scholar · View at Scopus
  165. Y. Jiang, W. Zhu, J. Zhu, L. Wu, G. Xu, and X. Liu, “Feasibility of delivering mesenchymal stem cells via catheter to the proximal end of lesion artery in patients with stroke in the territory of middle cerebral artery,” Cell Transplantation, vol. 22, no. 12, pp. 2291–2298.
  166. R. S. Lappalainen, S. Narkilahti, T. Huhtala et al., “The SPECT imaging shows the accumulation of neural progenitor cells into internal organs after systemic administration in middle cerebral artery occlusion rats,” Neuroscience Letters, vol. 440, no. 3, pp. 246–250, 2008. View at Publisher · View at Google Scholar · View at Scopus
  167. J. M. Levitt, I. J. Lodhi, P. K. Nguyen et al., “Low-dose sulfur mustard primes oxidative function and induces apoptosis in human polymorphonuclear leukocytes,” International Immunopharmacology, vol. 3, no. 5, pp. 747–756, 2003. View at Publisher · View at Google Scholar · View at Scopus
  168. B. Mitkari, E. Kerkela, J. Nystedt et al., “Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells results in transient localization in the brain after cerebral ischemia in rats,” Experimental Neurology, vol. 239, pp. 158–162, 2013. View at Google Scholar
  169. B. C. White, J. M. Sullivan, D. J. DeGracia et al., “Brain ischemia and reperfusion: molecular mechanisms of neuronal injury,” Journal of the Neurological Sciences, vol. 179, no. 1-2, pp. 1–33, 2000. View at Publisher · View at Google Scholar · View at Scopus
  170. H. J. Lee, K. S. Kim, I. H. Park, and S. U. Kim, “Human neural stem cells over-expressing VEGF provide neuroprotection, angiogenesis and functional recovery in mouse stroke model,” PLoS ONE, vol. 2, no. 1, article e156, 2007. View at Publisher · View at Google Scholar · View at Scopus
  171. H. J. Lee, M. K. Kim, H. J. Kim, and S. U. Kim, “Human neural stem cells genetically modified to overexpress Akt1 provide neuroprotection and functional improvement in mouse stroke model,” PLoS ONE, vol. 4, no. 5, Article ID e5586, 2009. View at Publisher · View at Google Scholar · View at Scopus
  172. H. Sakata, P. Narasimhan, K. Niizuma, C. M. Maier, T. Wakai, and P. H. Chan, “Interleukin 6-preconditioned neural stem cells reduce ischaemic injury in stroke mice,” Brain, vol. 135, pp. 3298–3310, 2012. View at Google Scholar
  173. M. Modo, K. Mellodew, D. Cash et al., “Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study,” NeuroImage, vol. 21, no. 1, pp. 311–317, 2004. View at Publisher · View at Google Scholar · View at Scopus
  174. W.-C. Shyu, C.-P. Chen, S.-Z. Lin, Y.-J. Lee, and H. Li, “Efficient tracking of non-iron-labeled mesenchymal stem cells with serial MRI in chronic stroke rats,” Stroke, vol. 38, no. 2, pp. 367–374, 2007. View at Publisher · View at Google Scholar · View at Scopus
  175. J. W. M. Bulte, T. Douglas, B. Witwer et al., “Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells,” Nature Biotechnology, vol. 19, no. 12, pp. 1141–1147, 2001. View at Publisher · View at Google Scholar · View at Scopus
  176. M. Rudelius, H. E. Daldrup-Link, U. Heinzmann et al., “Highly efficient paramagnetic labelling of embryonic and neuronal stem cells,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 30, no. 7, pp. 1038–1044, 2003. View at Publisher · View at Google Scholar · View at Scopus
  177. R. J. Ward, S. Wilmet, R. Legssyer, and R. R. Crichton, “The influence of iron homoeostasis on macrophage function,” Biochemical Society Transactions, vol. 30, no. 4, pp. 762–765, 2002. View at Publisher · View at Google Scholar · View at Scopus
  178. M. M. Khalil, J. L. Tremoleda, T. B. Bayomy, and W. Gsell, “Molecular SPECT imaging: an overview,” International Journal of Molecular Imaging, vol. 2011, Article ID 796025, 15 pages, 2011. View at Publisher · View at Google Scholar
  179. M. M. Lalu, L. McIntyre, C. Pugliese et al., “Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials,” PLoS ONE, vol. 7, no. 10, Article ID e47559, 2012. View at Google Scholar
  180. T. Nomura, O. Honmou, K. Harada, K. Houkin, H. Hamada, and J. D. Kocsis, “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, vol. 136, no. 1, pp. 161–169, 2005. View at Publisher · View at Google Scholar · View at Scopus
  181. Y. Horita, O. Honmou, K. Harada, K. Houkin, H. Hamada, and J. D. Kocsis, “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,” Journal of Neuroscience Research, vol. 84, no. 7, pp. 1495–1504, 2006. View at Publisher · View at Google Scholar · View at Scopus
  182. G.-W. Cho, S.-H. Koh, M.-H. Kim et al., “The neuroprotective effect of erythropoietin-transduced human mesenchymal stromal cells in an animal model of ischemic stroke,” Brain Research, vol. 1353, pp. 1–13, 2010. View at Publisher · View at Google Scholar · View at Scopus
  183. J. Ding, Y. Cheng, S. Gao, and J. Chen, “Effects of nerve growth factor and Noggin-modified bone marrow stromal cells on stroke in rats,” Journal of Neuroscience Research, vol. 89, no. 2, pp. 222–230, 2011. View at Publisher · View at Google Scholar · View at Scopus