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  • 1 Department of Neurosurgery and Brain Repair, University of South Florida, College of Medicine, Tampa, FL, USA
  • | 2 Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
  • | 3 Cryo-Cell International, Inc., Tampa, FL, USA
  • | 4 Saneron-CCEL Therapeutics Inc., Tampa, FL, USA
  • | 5 Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida, College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA
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Abstract

Cerebrovascular diseases are a major cause of death and long-term disability in developed countries. Tissue plasmin activator (tPA) is the only approved therapy for ischemic stroke, strongly limited by the short therapeutic window and hemorrhagic complications, therefore excluding most patients from its benefits. The rescue of the penumbra area of the ischemic infarct is decisive for functional recovery after stroke. Inflammation is a key feature in the penumbra area and it plays a dual role, improving injury in early phases but impairing neural survival at later stages. Stem cells can be opportunely used to modulate inflammation, abrogate cell death and, therefore, preserve neural function. We here discuss the possible role of stem cells derived from menstrual blood as restorative treatment for stroke. We highlight the availability, proliferative capacity, pluripotentiality and angiogenic features of these cells and explore their present and future experimental and clinical applications.

  • 1. J. Xu et al. 2010 Deaths, final data for 2007 National Vital Statistics Reports 57 1 134.

  • 2. Centers for Disease ControlPrevention 1999 Prevalence of disabilities and associated health conditions among adults United States. M.M.W.R. Morb Mortal Wkly Rep 50 120 125.

    • Search Google Scholar
    • Export Citation
  • 3. K. Asplund B. Stegmayr M. Peltonen 1998 From the twentieth to the twenty-first century: A public health perspective on stroke M.D. Ginsberg J. Bogousslavsky Cerebrovascular Disease Pathophysiology, Diagnosis, and Management Blackwell Science MA, USA.

    • Search Google Scholar
    • Export Citation
  • 4. A.V. Alexandrov et al. 2001 Speed of intracranial clot lysis with intravenous tissue plasminogen activator therapy, sonographic classification and short-term improvement Circulation 103 2897 2902.

    • Search Google Scholar
    • Export Citation
  • 5. J.R. Marler et al. 2000 Early stroke treatment associated with better outcome, the NINDS rt-PA stroke study Neurology 55 1649 1655.

  • 6. J.H. Rha J.L. Saver 2007 The impact of recanalization on ischemic stroke outcome? A meta-analysis. Stroke 38 967 973.

  • 7. The National Institute of Neurological DisordersStroke 1995 tissue plasminogen activator for acute ischemic stroke N Engl J Med 333 1581 1587.

    • Search Google Scholar
    • Export Citation
  • 8. W. Hacke et al. 1995 Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS) J.A.M.A. 274 1017 1025.

    • Search Google Scholar
    • Export Citation
  • 9. D. Kleindorfer et al. 2008 National US estimates of recombinant tissue plasminogen activator use, ICD-9 codes substantially underestimate Stroke 39 924 928.

    • Search Google Scholar
    • Export Citation
  • 10. C.R. Carpenter et al. 2011 The Best Evidence in Emergency Medicine Investigator Group. Thrombolytic therapy for acute ischemic stroke beyond 3 hours J Emerg Med 40 82 92.

    • Search Google Scholar
    • Export Citation
  • 11. C.A. Cronin 2010 Intravenous tissue plasminogen activator for stroke, a review of the ECASS III results in relation to prior clinical trials J Emer Med 38 99 105.

    • Search Google Scholar
    • Export Citation
  • 12. W. Hacke et al. 2008 Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke N Engl J Med 359 1317 1329.

  • 13. J.C. Chavez et al. 2010 Pharmacologic interventions for stroke: looking beyond the thrombolysis time window into the penumbra with biomarkers, not a stopwatch Stroke 40 e558 e563.

    • Search Google Scholar
    • Export Citation
  • 14. R.A. Green et al. 2003 Animal models of stroke: do they have value for discovering neuroprotective agents? Trends Pharmacol Sci 24 402 408.

    • Search Google Scholar
    • Export Citation
  • 15. NINDS 2000 The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group: Effect of intravenous recombinant tissue plasminogen activator on ischemic stroke lesion size measured by computed tomography Stroke 31 2912 2919.

    • Search Google Scholar
    • Export Citation
  • 16. D.C. Hess C.V. Borlongan 2008 Cell-based therapy in ischemic stroke Expert Rev Neurother 8 1193 1201.

  • 17. W.D. Hill et al. 2004 SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury J Neuropathol Exp Neurol 63 84 96.

    • Search Google Scholar
    • Export Citation
  • 18. D.W. Choi S.M. Rothman 1990 The role of gutamete neurotoxicity in hypoxic-ischemic neuronal death Annu Rev Neurosci 13 171 182.

  • 19. M. Ankarcrona et al. 1995 Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function Neuron 15 961 973.

    • Search Google Scholar
    • Export Citation
  • 20. E. Besancon et al. 2008 Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke Trends Pharmacol Sci 29 268 277.

    • Search Google Scholar
    • Export Citation
  • 21. S. Amor et al. 2010 Inflammation in neurodegenerative diseases Immunology 129 154 169.

  • 22. C.A. Emsley et al. 2008 Inflammation in acute ischemic stroke and its relevance to stroke critical care Neurocrit Care 9 125 138.

  • 23. J. Koenigsknecht G. Landreth 2004 Microglial phagocytosis of fibrillar beta-amyloid through a beta1 integrin-dependent mechanism J Neurosci 24 9838 9846.

    • Search Google Scholar
    • Export Citation
  • 24. T. Takano et al. 2009 Astrocytes and ischemic injury Stroke 40 Suppl.3 S8 S12.

  • 25. J.R. Faulkner et al. 2004 Reactive astrocytes protect tissue and preserve function after spinal cord injury J Neurosci 24 2143 2155.

  • 26. J. Kriz 2006 Inflammation in ischemic brain injury, timing is important Crit Rev Neurobiol 18 145 157.

  • 27. Y. Zhao D.A. Rempe 2010 Targeting astrocytes for stroke therapy Neurotherapeutic 7 439 451.

  • 28. C.V. Borlongan et al. 2004 Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke Stroke 35 2385 2389.

    • Search Google Scholar
    • Export Citation
  • 29. H. Felfly et al. 2010 Hematopoietic stem cell transplantation protects mice from lethal stroke Exp Neurol 225 284 293.

  • 30. E. Keimpema et al. 2009 Early transient presence of implanted bone marrow stem cells reduces lesion size after cerebral ischaemia in adult rats Neuropathol Appl Neurobiol 35 89 102.

    • Search Google Scholar
    • Export Citation
  • 31. S. Schwarting et al. 2008 Hematopoietic stem cells reduce post-ischemic inflammation and ameliorate ischemic brain injury Stroke 39 2867 2875.

    • Search Google Scholar
    • Export Citation
  • 32. J. Wu et al. 2008 Intravenously administered bone marrow cells migrate to damaged brain tissue and improve neural function in ischemic rats Cell Transplant 16 993 1005.

    • Search Google Scholar
    • Export Citation
  • 33. S.H. Koh et al. 2008 Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats Brain Res 229 233 248.

    • Search Google Scholar
    • Export Citation
  • 34. Y.P. Liu et al. 2009 The potential of neural stem cells to repair strokeinduced brain damage Acta Neuropathol 117 469 480.

  • 35. C.V. Borlongan et al. 1998 Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats Exp Neurol 149 310 321.

    • Search Google Scholar
    • Export Citation
  • 36. K. Jin et al. 2005 Comparison of ischemia-directed migration of neural precursor cells after intrastriatal, intraventricular, or intravenous transplantation in the rat Neurobiol Dis 18 366 374.

    • Search Google Scholar
    • Export Citation
  • 37. Y. Takagi et al. 2004 Survival and differentiation of neural progenitor cells derived from embryonic cells and transplanted into ischemic brain J Neurosurg 103 304 310.

    • Search Google Scholar
    • Export Citation
  • 38. A. Taguchi et al. 2004 Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model J Clin Invest 114 330 338.

    • Search Google Scholar
    • Export Citation
  • 39. A. Saghatelyan 2009 Role of blood vessels in the neuronal migration Semin Cell Dev Biol 20 744 750.

  • 40. Y. Fan et al. 2010 Endothelial progenitor cell transplantation improves long-term stroke outcome in mice Ann Neurol 67 488 497.

  • 41. N. Nakagomi et al. 2009 Endothelial cells support survival, proliferation, and neuronal differentiation of transplanted adult ischemia-induced neural stem/progenitor cells after cerebral infarction Stem Cells 9 2185 2195.

    • Search Google Scholar
    • Export Citation
  • 42. R. Barzilay et al. 2006 Adult stem cells for neuronal repair Isr Med Assoc J 8 61 66.

  • 43. F. Hefti 1997 Pharmacology of neurotrophic factors Annu Rev Pharmacol Toxicol 37 239 267.

  • 44. A.J. Loughlin et al. 1993 Modulation of interferon-gamma-induced major histocompatibility complex class II and Fc receptor expression on isolated microglia by transforming growth factorbeta 1, interleukin-4, noradrenaline and glucocorticoids Immunology 79 125 130.

    • Search Google Scholar
    • Export Citation
  • 45. B. Connor M. Dragunow 1998 The role of neuronal growth factors in neurodegenerative disorders of the human brain Brain Res Rev 27 1 39.

    • Search Google Scholar
    • Export Citation
  • 46. E.S. Connolly Jr et al. 1996 Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke J Clin Invest 97 209 216.

    • Search Google Scholar
    • Export Citation
  • 47. P.D. Hurn et al. 2007 T- and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation J Cereb Blood Flow Metab 27 1798 1805.

    • Search Google Scholar
    • Export Citation
  • 48. S. Banwell et al. 2009 Systematic review and stratified meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke J Stroke Cerebrovasc Dis 18 269 276.

    • Search Google Scholar
    • Export Citation
  • 49. H. Fan et al. 2009 Oxymatrine downregulates TLR4, TLR2, MyD88, and NF-kappaB and protects rat brains against focal ischemia Mediators Inflamm 2009 704 706.

    • Search Google Scholar
    • Export Citation
  • 50. X. Wang et al. 2004 Inhibition of tumor necrosis factor-alpha-converting enzyme by a selective antagonist protects brain from focal ischemic injury in rats Mol Pharmacol 65 890 896.

    • Search Google Scholar
    • Export Citation
  • 51. G. Yilmaz D.N. Granger 2010 Leukocyte recruitment and ischemic brain injury Neuromolecular Med 12 193 204.

  • 52. Enlimomab Acute Stroke Trial Investigators 2001 Use of anti-ICAM-1 therapy in ischemic stroke: results of the Enlimomab Acute Stroke Trial Neurology 57 1428 1434.

    • Search Google Scholar
    • Export Citation
  • 53. J. Faraji et al. 2009 Stress and corticosterone enhance cognitive recovery from hippocampal stroke in rats Neurosci Lett 462 248 252.

  • 54. G. Linares S.A. Mayer 2009 Hypothermia for the treatment of ischemic and hemorrhagic stroke Crit Care Med 37 S243 S249.

  • 55. N. Matsukawa et al. 2009 Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke B.M.C. Neurosci 10 126.

    • Search Google Scholar
    • Export Citation
  • 56. S.T. Lee et al. 2008 Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke Brain 131 616 629.

    • Search Google Scholar
    • Export Citation
  • 57. S.Y. Kim et al. 2009 Soluble mediators from human neural stem cells play a critical role in suppression of T-cell activation and proliferation J Neurosci Res 87 2264 2272.

    • Search Google Scholar
    • Export Citation
  • 58. P.R. Baraniak T.C. McDevitt 2010 Stem cell paracrine actions and tissue regeneration Regen Med 5 121 143.

  • 59. S. Banerjee et al. 2011 Human stem cell therapy in ischaemic stroke: a review Age Ageing 40 7 13.

  • 60. D.H. Park et al. 2009 Inflammation and stem cell migration to the injured brain in higher organisms Stem Cells Dev 18 693 701.

  • 61. J.E. Le Belle et al. 2004 Improving the survival of human CNS precursor-derived neurons after transplantation J Neurosci Res 76 174 183.

  • 62. Y. Fujiwara et al. 2004 Intravenously injected neural progenitor cells of transgenic rats can migrate to the injured spinal cord and differentiate into neurons, astrocytes and oligodendrocytes Neurosci Lett 366 287 291.

    • Search Google Scholar
    • Export Citation
  • 63. A. Jablonska et al. 2010 Transplantation of neural stem cells derived from human cord blood to the brain of adult and neonatal rats Acta Neurobiol Exp 70 337 350.

    • Search Google Scholar
    • Export Citation
  • 64. D. Mitrecić et al. 2010 Distribution, differentiation, and survival of intravenously administered neural stem cells in a rat model of amyotrophic lateral sclerosis Cell Transplant 19 537 548.

    • Search Google Scholar
    • Export Citation
  • 65. L. Sun et al. 2004 Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury J Clin Invest 113 1364 1374.

    • Search Google Scholar
    • Export Citation
  • 66. D.H. Park et al. 2009 Human umbilical cord blood cell grafts for brain ischemia Cell Transplant 18 985 998.

  • 67. J. Ourednik et al. 2002 Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons Nat Biotechnol 20 1103 1110.

  • 68. T. Yasuhara et al. 2006 Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson's disease J Neurosci 26 12497 12511.

    • Search Google Scholar
    • Export Citation
  • 69. A.S. Daar et al. 2004 Stem cell research and transplantation: science leading ethics Transplant Proc 36 2504 2506.

  • 70. T. Umemura et al. 2008 Aging and hypertension are independent risk factors for reduced number of circulating endothelial progenitor cells Am J Hypertens 21 1203 1209.

    • Search Google Scholar
    • Export Citation
  • 71. W. Wagner et al. 2009 Aging and replicative senescence have related effects on human stem and progenitor cells PLoS One 4 e5846.

  • 72. K. Tan et al. 2010 Impaired function of circulating CD34(+) CD45(−) cells in patients with proliferative diabetic retinopathy Exp Eye Res 91 229 237.

    • Search Google Scholar
    • Export Citation
  • 73. J.A. Govaert et al. 2009 Poor functional recovery after transplantation of diabetic bone marrow stem cells in ischemic myocardium J Heart Lung Transplant 28 1158 1165.

    • Search Google Scholar
    • Export Citation
  • 74. Antonucci I et al.: Amniotic fluid as rich source of mesenchymal cells for transplantation therapy. Cell Transplant Nov 5 [Epub ahead of print, doi:] (2010).

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 75. A.N. Patel et al. 2008 Multipotent menstrual blood stromal stem cells, isolation, characterization and differentiation Cell Transplant 17 303 311.

    • Search Google Scholar
    • Export Citation
  • 76. H. Yagi et al. 2010 Mesenchymal stem cells: mechanisms of immunomodulation and homing Cell Transplant 19 667 679.

  • 77. J. Westrich et al. 2010 Factors affecting residence time of mesenchymal stromal cells (MSC) injected into the myocardium Cell Transplant 19 937 948.

    • Search Google Scholar
    • Export Citation
  • 78. S. Gerbal-Chaloin et al. 2010 Isolation and culture of adult human liver progenitor cells, in vitro differentiation to hepatocyte-like cells Methods Mol Biol 640 247 260.

    • Search Google Scholar
    • Export Citation
  • 79. H.I. Huang et al. 2010 Multilineage differentiation potential of fibroblast-like stromal cells derived from human skin Tissue Eng Part A 16 1491 1501.

    • Search Google Scholar
    • Export Citation
  • 80. F. Mosna et al. 2010 Cell therapy for cardiac regeneration after myocardial infarct, which cell is the best? Cardiovasc Hematol Agents Med Chem 8 227 243.

    • Search Google Scholar
    • Export Citation
  • 81. V.A. Prianishnikov 1978 On the concept of stem cell and a model of functional-morphological structure of the endometrium Contraception 18 213 223.

    • Search Google Scholar
    • Export Citation
  • 82. H.A. Padykula 1991 Regeneration in the primate uterus, the role of stem cells Ann N Y Acad Sci 622 47 52.

  • 83. R.W. Chan et al. 2004 Clonogenicity of human endometrial epithelial and stromal cells Biol Reprod 70 1738 1750.

  • 84. X. Meng et al. 2007 Endometrial regenerative cells: a novel stem cell population J Transl Med 5 57.

  • 85. I. Cervelló et al. 2010 Human endometrial side population cells exhibit genotypic, phenotypic and functional features of somatic stem cells PLoS One 5 e10964.

    • Search Google Scholar
    • Export Citation
  • 86. H. Masuda et al. 2010 Human endometrial stem cells PLoS One 5 e10387.

  • 87. M.P. Murphy et al. 2008 Allogeneic endometrial regenerative cells, an “off the shelf solution” for critical limb ischemia? J Transl 6 45.

    • Search Google Scholar
    • Export Citation
  • 88. H.S. Taylor 2004 Endometrial cells derived from donor stem cells in bone marrow transplant recipients J.A.M.A. 292 80 85.

  • 89. E.F. Wolff et al. 2011 Endometrial stem cell transplantation restores dopamine production in a Parkinson's disease model J Cell Mol Med 15 747 755.

    • Search Google Scholar
    • Export Citation
  • 90. A. Bratincsák et al. 2007 CD45-positive blood cells give rise to uterine epithelial cells in mice Stem Cells 25 2820 2826.

  • 91. N. Hida et al. 2008 Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells Stem Cells 26 1695 1704.

  • 92. H. Drago et al. 2010 The next generation of burns treatment, intelligent films and matrix, controlled enzymatic debridement, and adult stem cells Transplant Proc 42 345 349.

    • Search Google Scholar
    • Export Citation
  • 93. C.V. Borlongan et al. 2010 Menstrual blood cells display stem celllike phenotypic markers and exert neuroprotection following transplantation in experimental stroke Stem Cells Dev 19 439 451.

    • Search Google Scholar
    • Export Citation
  • 94. N.H. Cho et al. 2004 Lifetime expression of stem cell markers in the uterine endometrium Fertil Steril 81 403 407.

  • 95. Z. Zhong et al. 2009 Feasibility investigation of allogeneic endometrial regenerative cells J Transl Med 7 15.

  • 96. C.E. Gargett et al. 2009 Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium Biol Reprod 80 1136 1145.

    • Search Google Scholar
    • Export Citation
  • 97. J.G. Allickson et al. 2011 Recent studies assessing the proliferative capability of a novel adult stem cell identified in menstrual blood Open Stem Cell J 3 4 10.

    • Search Google Scholar
    • Export Citation
  • 98. M. Mazo et al. 2008 Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction Eur J Heart Fail 10 454 462.

    • Search Google Scholar
    • Export Citation
  • 99. M.H. Moon et al. 2006 Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia Cell Physiol Biochem 17 279 290.

    • Search Google Scholar
    • Export Citation
  • 100. H. Nakagami et al. 2005 Novel autologous cell therapy in ischemic limb disease through growth factor secretion by cultured adipose tissue-derived stromal cells Arterioscler Thromb Vasc Biol 25 2542 2547.

    • Search Google Scholar
    • Export Citation
  • 101. Y. Ikegame et al. 2011 Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy Cytotherapy 13 675 685.

    • Search Google Scholar
    • Export Citation
  • 102. S.K. Kang et al. 2006 Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury Stem Cells Dev 15 583 594.

  • 103. J.K. Ryu et al. 2009 Neural progenitor cells attenuate inflammatory reactivity and neuronal loss in an animal model of inflamed AD brain J Neuroinflammation 6 39.

    • Search Google Scholar
    • Export Citation
  • 104. W. Xuqian et al. 2011 Intraocular transplantation of human adiposederived mesenchymal stem cells in a rabbit model of experimental retinal holes Ophthalmic Res 46 199 207.

    • Search Google Scholar
    • Export Citation
  • 105. I. V. Poliachenko et al. 2010 Ultrastructural changes of vascular endothelium in patients with chronic ischemia of the extremities after conduction of multipotent stromal cells from adipose tissue transplantation Klin Khir 6 50 53.

    • Search Google Scholar
    • Export Citation
  • 106. Ra JC et al.: Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev (2011) [Epub ahead of print, doi: ].

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 107. S. Kern et al. 2006 Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue Stem Cells 24 1294 1301.

    • Search Google Scholar
    • Export Citation
  • 108. M.J. Zhang et al. 2009 Could cells from menstrual blood be a new source for cell-based therapies? Med Hypotheses 72 252 254.

  • 109. C.H. Cui et al. 2007 Menstrual blood-derived cells confer human dystrophin expression in the murine model of Duchenne muscular dystrophy via cell fusion and myogenic transdifferentiation Mol Biol Cell 18 1586 1594.

    • Search Google Scholar
    • Export Citation
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