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Stem cell therapy for neurological disorders

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  • Translational Neuroscience
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Translational Neuroscience

Abstract

Stem cells have long been in focus as potential therapy or even cure for a whole myriad of diseases. Many neurodegenerative disorders, both acute and chronic, are characterized by irreversible neuronal damage and loss, and only a few efficient treatment options exist. In contrast to many other tissues, the potential of self-regeneration of the central nervous system is highly limited. There is hope that stem cells could replace the damaged neuronal and glial cells, and provide biological and functional restoration based on their properties of self renewal and the ability to give rise to different cells. In recent years, the promising results of research on animal models has led to the establishment of the first clinical trials; although no clear evidence of therapeutic benefit for any of the conditions have been ascertained. Here we give a review of the current strategies of stem-cell based therapy for some of the more common neurological disorders, discussing the progress and current challenges, and giving an overview of future perspectives.

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References

  1. Park D. H., Eve D. J., Chung Y. G., Sanberg P. R., Regenerative medicine for neurological disorders, ScientificWorldJournal, 2010, http://www. tswj.com/2010/463612/abs/

  2. Srivastava A. S., Malhotra R., Sharp J., Berggren T., Potentials of ES cell therapy in neurodegenerative diseases, Curr. Pharm. Design., 2008, 14, 3873–3879

    Article  CAS  Google Scholar 

  3. Takahashi K., Yamanaka S., Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors, Cell, 2006, 126, 663–676

    Article  PubMed  CAS  Google Scholar 

  4. Baker M., Stem cells: Fast and furious, Nature, 2009, 458, 462–465

    Article  Google Scholar 

  5. Mattis V. B., Svendsen C. N., Induced pluripotent stem cells: a new revolution for clinical neurology?, Lancet Neurol., 2011, 10, 383–394

    Article  PubMed  Google Scholar 

  6. Park I. H., Arora N., Huo H., Maherali N., Ahfeldt T., Shimamura A. et al., Disease specific induced pluripotent stem cells, Cell, 2008, 134, 877–886

    Article  PubMed  CAS  Google Scholar 

  7. Durnaoglu S., Genc S., Genc K., Patient-specific pluripotent stem cells in neurological diseases, Stem Cells Int., 2011, http://www.hindawi.com/journals/sci/2011/212487/

  8. Doetsch F., Caille I., Lim D.A., Garcia-Verdugo J.M., Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain, Cell 97, 1999, 703–716

    Article  PubMed  CAS  Google Scholar 

  9. Reynolds B. A., Weiss S., Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system, Science, 1992, 255, 1707–1710

    Article  PubMed  CAS  Google Scholar 

  10. Eriksson P. S., Perfilieva E., Bjork-Eriksson T., Alborn A. M., Nordborg C., Peterson D. A. et al., Neurogenesis in the adult human hippocampus, Nat. Med., 1998, 4, 1313–1317

    Article  PubMed  CAS  Google Scholar 

  11. Alvarez-Buylla A., García-Verdugo J. M., Tramontin A. D., A unified hypothesis on the lineage of neural stem cells, Nat. Rev. Neurosci., 2001, 2, 287–293

    Article  PubMed  CAS  Google Scholar 

  12. Kempermann G., Wiskott L., Gage F. H., Functional significance of adult neurogenesis, Curr. Opin. Neurobiol., 2004, 14, 186–191

    Article  PubMed  CAS  Google Scholar 

  13. Kempermann G. Seven principles in the regulation of adult neurogenesis. Eur J Neurosci., 2011, 33, 1018–24

    Article  PubMed  Google Scholar 

  14. Zhao C., Deng W., Gage F. H., Mechanisms and functional implications of adult neurogenesis, Cell, 2008, 132, 645–660

    Article  PubMed  CAS  Google Scholar 

  15. Jin K., Sun Y., Xie L., Peel A., Mau X. O., Batteur S. et al., Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum, Mol. Cell. Neurosci., 2003, 24, 171–189

    Article  PubMed  CAS  Google Scholar 

  16. Emery D. L., Fulp C. T., Saatman K. E., Schutz C., Neugebauer E., McIntosh T. K., Newly born granule cells in the dentate gyrus rapidly extend axons into the hippocampal CA3 region following experimental brain injury, J. Neurotrauma, 2005, 22, 978–988

    Article  PubMed  Google Scholar 

  17. Picard-Riera N., Decker L., Delarasse C., Goude K., Nait-Oumesmar B., Liblau R. et al., Experimental autoimmune encephalomyelitis mobilized neuronal progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice, Proc. Natl. Acad. Sci. U S A, 2002, 99, 13211–13216

    Article  PubMed  CAS  Google Scholar 

  18. Hattiangady B., Shuai B., Cai J., Coksaygan T., Rao M. S., Shetty A. K., Increased dentate neurogenesis after grafting of glial restricted progenitors or neural stem cells in the aging hippocampus, Stem cells, 2007, 25, 2104–2117

    Article  PubMed  Google Scholar 

  19. Munoz J. R., Stoutenger B. R., Robinson A. P., Spees J. L., Prockop D. J., Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice, Proc. Natl. Acad. Sci. U S A, 2005, 102, 18171–18176, Erratum in: Proc. Natl. Acad. Sci. U S A, 2006, 103, 2000–2002

    Article  PubMed  CAS  Google Scholar 

  20. Martino G., Pluchino S., The therapeutic potential of neural stem cells, Nat. Rev. Neurosci., 2006, 7, 395–406

    Article  PubMed  CAS  Google Scholar 

  21. Lindvall O., Kokaia Z., Stem cells for the treatment of neurological disorders, Nature, 2006, 441, 1094–1096

    Article  PubMed  CAS  Google Scholar 

  22. Lindvall O., Kokaia Z., Stem cells in human neurodegenerative disorders—time for clinical translation?, J. Clin. Invest., 2010, 120, 29–40

    Article  PubMed  CAS  Google Scholar 

  23. Polgar S., Morris M. E., Reilly S., Bilney B., Sanberg P. R., Reconstructive neurosurgery for Parkinson’s disease: a systematic review and preliminary meta-analysis, Brain Res. Bull., 2003, 60, 1–24

    Article  PubMed  CAS  Google Scholar 

  24. Lindvall O., Björklund A., Cell therapy in Parkinson’s disease, NeuroRx., 2004, 1, 382–393

    Article  PubMed  Google Scholar 

  25. Brazzini A., Cantella R., De la Cruz A., Yupanqui J., León C., Jorquiera T. et al., Intraarterial autologous implantation of adult stem cells for patients with Parkinson disease, J. Vasc. Interv. Radiol., 2010, 21, 443–451

    Article  PubMed  Google Scholar 

  26. Venkataramana N. K., Kumar S. K., Balaraju S., Radhakrishnan R. C., Bansal A., Dixit A. et al., Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease, Transl. Res., 2010, 155, 62–70

    Article  PubMed  CAS  Google Scholar 

  27. Lévesque M. F., Neuman T., Rezak M., Therapeutic microinjection of autologous adult human neural stem cells and differentiated neurons for Parkinson’s disease: five-year post-operative outcome, Open Stem Cell J., 2009, http://benthamscience.com/open/toscj/openaccess2.htm

  28. Hagell P., Piccini P., Björklund A., Brundin P., Rehncrona S., Widner H. et al., Dyskinesias following neural transplantation in Parkinson’s disease, Nat. Neurosci., 2002, 5, 627–628

    PubMed  CAS  Google Scholar 

  29. Lang A. E., Obeso J. A., Challenges in Parkinson’s disease: restoration of the nigrostriatal dopamine system is not enough, Lancet Neurol., 2004, 3, 309–316

    Article  PubMed  Google Scholar 

  30. Behrstock S., Ebert A., McHugh J., Vosberg S., Moore J., Schneider B. et al., Human neural progenitors deliver glial cell line-derived neurotrophc factor to parkinsonian rodents and aged primates, Gene Ther., 2006, 13, 379–388

    Article  PubMed  CAS  Google Scholar 

  31. Bachoud-Lévi A. C., Gaura V., Brugières P., Lefaucheur J. P., Boissé M. F., Maison P. et al., Effect of fetal neural transplants in patients with Huntington’s disease 6 years after surgery: a long-term follow-up study, Lancet Neurol., 2006, 5, 303–309

    Article  PubMed  Google Scholar 

  32. Lescaudron L., Unni D., Dunbar G. L., Autologous adult bone marrow stem cell transplantation in an animal model of Huntington’s disease: behavioral and morphological outcomes, Int. J. Neurosci., 2003, 113, 945–956

    Article  PubMed  Google Scholar 

  33. McBride J. L., Behrstock S. P., Chen E. Y., Jakel R. J., Siegel I., Svendsen C. N. et al., Human neural stem cell transplants improve motor function in a rat model of Huntington’s disease, J. Comp. Neurol., 2004, 475, 211–219

    Article  PubMed  Google Scholar 

  34. Ebert A. D., Barber A. E., Heins B. M., Svendsen C. N., Ex vivo delivery ofGDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington’s disease, Exp. Neurol., 2010, 224, 155–162

    Article  PubMed  CAS  Google Scholar 

  35. Silani V., Cova L., Corbo M., Ciammola A., Polli E., Stem-cell therapy for amyotrophic lateral sclerosis, Lancet, 2004, 364, 200–202

    Article  PubMed  Google Scholar 

  36. Borchelt D. R., Amyotrophic lateral sclerosis-are microglia killing motor neurons?, N. Engl. J. Med., 2006, 12, 1611–1613

    Article  Google Scholar 

  37. Clement A. M., Nguyen M. D., Roberts E. A., Garcia M. L., Boillée S., Rule M. et al., Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice, Science, 2003, 302, 113–117

    Article  PubMed  CAS  Google Scholar 

  38. Lepore A. C., Rauck B., Dejea C., Pardo A. C., Rao M.S., Rothstein J. D. et al., Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease, Nat. Neurosci, 2008, 11, 1294–1301

    Article  PubMed  CAS  Google Scholar 

  39. Mazzini L., Ferrero I., Luparello V., Rustichelli D., Gunetti M., Mareschi K. et al., Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial, Exp. Neurol., 2010, 223, 229–237

    Article  PubMed  CAS  Google Scholar 

  40. Martinez H. R., Gonzalez-Garza M. T., Moreno-Cuevas J. E., Caro E., Gutierrez-Jimenez E., Segura J. J., Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients, Cytotherapy, 2009, 11, 26–34

    Article  PubMed  CAS  Google Scholar 

  41. Deda H., Inci M. C., Kürekçi A. E., Sav A., Kayihan K., Ozgün E., Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up, Cytotherapy, 2009, 11, 18–25

    Article  PubMed  CAS  Google Scholar 

  42. Karussis D., Karageorgiou C., Vaknin-Dembinsky A., Gowda-Kurkalli B., Gomori J. M., Kassis I. et al., Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis, Arch. Neurol., 2010, 67, 1187–1194

    Article  PubMed  Google Scholar 

  43. Lunn J. S., Sakowski S. A., Hur J., Feldman E. L., Stem cell technology for neurodegenerative diseases, Ann. Neurol., 2011, 70, 353–361

    Article  PubMed  CAS  Google Scholar 

  44. Martino G., Franklin R. J., Van Evercooren A. B., Kerr D. A., Stem Cells in Multiple Sclerosis (STEMS) Consensus Group. Stem cell transplantation in multiple sclerosis: current status and future prospects, Nat. Rev. Neurol., 2010, 6, 247–255

    Article  PubMed  Google Scholar 

  45. Scolding N., Adult stem cells and multiple sclerosis, Cell Prolif., 2011, 44(Suppl. 1), 35–38

    Article  PubMed  Google Scholar 

  46. Fassas A., Anagnostopoulos A., Kazis A., Kapinas K., Sakellari I., Kimiskidis V. et al., Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study, Bone Marrow Transplant., 1997, 20, 631–638

    Article  PubMed  CAS  Google Scholar 

  47. Fassas A., Passweg J. R., Anagnostopoulos A., Kazis A., Kozak T., Havrdova E. et al., Autoimmune disease working party of the EBMT (European Group for Blood and Marrow Transplantation). Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study, J. Neurol., 2002, 249, 1088–1097

    Article  PubMed  CAS  Google Scholar 

  48. Fassas A., Kimiskidis V. K., Sakellari I., Kapinas K., Anagnostopoulos A., Tsimourtou V. et al., Long-term results of stem cell transplantation for MS: a single-center experience, Neurology, 2011, 76, 1066–1070

    Article  PubMed  CAS  Google Scholar 

  49. Burt R. K., Loh Y., Cohen B., Stefoski D., Balabanov R., Katsamakis G. et al., Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study, Lancet Neurol., 2009, 8, 244–253, Erratum in: Lancet Neurol., 2009, 8, 309

    Article  PubMed  CAS  Google Scholar 

  50. Cummings B. J., Uchida N., Tamaki S. J., Salazar D. L., Hooshmand M., Summers R. et al., Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice, Proc. Natl. Acad. Sci. U S A, 2005, 102, 14069–14074

    Article  PubMed  CAS  Google Scholar 

  51. Keirstead H. S., Nistor G., Bernal G., Totoiu M., Cloutier F., Sharp K. et al., Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury, J. Neurosci., 2005, 25, 4694–4705

    Article  PubMed  CAS  Google Scholar 

  52. Lee S. H., Chung Y. N., Kim Y. H., Kim Y. J., Park J. P., Kwon D. K. et al., Effects of human neural stem cell transplantation in canine spinal cord hemisection, Neurol. Res., 2009, 31, 996–1002

    Article  PubMed  Google Scholar 

  53. Sharp J., Frame J., Siegenthaler M., Nistor G., Keirstead H. S., Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury, Stem Cells, 2010, 28, 152–163

    PubMed  CAS  Google Scholar 

  54. Pal R., Venkataramana N. K., Bansal A., Balaraju S., Jan M., Chandra R. et al., Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study, Cytotherapy, 2009, 11, 897–911

    Article  PubMed  CAS  Google Scholar 

  55. Yoon S. H., Shim Y. S., Park Y. H., Chung J. K., Nam J. H., Kim M. O. et al., Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial, Stem Cells, 2007, 25, 2066–2073

    Article  PubMed  Google Scholar 

  56. Hofstetter C. P., Holmstrom N. A., Lilja J. A., Schweinhardt P., Hao J., Spenger C. et al., Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome, Nat. Neurosci., 2005, 8, 346–353

    Article  PubMed  CAS  Google Scholar 

  57. Macias M. Y., Syring M. B., Pizzi M. A., Crowe M. J., Alexanian A. R., Kurpad S.N. Pain with no gain: Allodynia following neural stem cell transplantation in spinal cord injury, Exp. Neurol., 2006, 201, 335–348

    Article  PubMed  CAS  Google Scholar 

  58. Thored P., Arvidsson A., Cacci E., Ahlenius H., Kallur T., Darsalia V. et al., Persistent production of neurons from adult brain stem cells during recovery after stroke, Stem Cells, 2006, 24, 739–747

    Article  PubMed  CAS  Google Scholar 

  59. Luo Y., Cell-based therapy for stroke, J. Neural. Transm., 2011, 118, 61–74

    Article  PubMed  Google Scholar 

  60. Shyu W. C., Lee Y. J., Liu D. D., Lin S. Z., Li H., Homing genes, cell therapy and stroke, Front. Biosci., 2006, 11, 899–907

    Article  PubMed  CAS  Google Scholar 

  61. Borlongan C. V., Hadman M., Sanberg C. D., Sanberg P. R., Central nervous system entry of peripherally injected umbilical cord blood cells is not required for neuroprotection in stroke, Stroke, 2004, 35, 2385–2389

    Article  PubMed  Google Scholar 

  62. Bliss T., Guzman R., Daadi M., Steinberg G. K., Cell transplantation therapy for stroke, Stroke, 2007, 38(Suppl. 2), 817–826

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  64. Savitz S. I., Dinsmore J., Wu J., Henderson G. V., Stieg P., Caplan L. R., Neurotransplantation of fetal porcine cells in patients with basal ganglia infarcts: a preliminary safety and feasibility study, Cerebrovasc. Dis., 2005, 20, 101–107

    Article  PubMed  Google Scholar 

  65. Bang O. Y., Lee J. S., Lee P. H., Lee G., Autologous mesenchymal stem cell transplantation in stroke patients, Ann. Neurol., 2005, 57, 874–882

    Article  PubMed  Google Scholar 

  66. Honmou O., Houkin K., Matsunaga T., Niitsu Y., Ishiai S., Onodera R. et al., Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke, Brain, 2011, 134, 1790–1807

    Article  PubMed  Google Scholar 

  67. Lee J. S., Hong J. M., Moon G. J., Lee P. H., Ahn Y. H., Bang O. Y. et al., A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke, Stem Cells, 2010, 28, 1099–1106

    Article  PubMed  Google Scholar 

  68. Chopp M., Li Y., Treatment of stroke and intracerebral hemorrhage with cellular and pharmacological restorative therapies, Acta Neurochir. Suppl., 2008, 105, 79–83

    Article  PubMed  CAS  Google Scholar 

  69. Shyu W. C., Lin S. Z., Lee C. C., Liu D. D., Li H., Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial, CMAJ, 2006, 174, 927–933

    Article  PubMed  Google Scholar 

  70. Tang K. C., Trzaska K. A., Smimov S., Kotenko S. V., Schwander S. K., Ellner J. J. et al., Down-regulation of MHC-II in mesenchimal stem cells at high IFN can be partly explained by cytoplasmic retention of CIITA, J. Immunol., 2008, 180, 1826–1833

    PubMed  CAS  Google Scholar 

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Correspondence to Koraljka Bačić Baronica.

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Baronica, K.B., Friedrich, L. Stem cell therapy for neurological disorders. Translat.Neurosci. 2, 319–324 (2011). https://doi.org/10.2478/s13380-011-0040-3

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