Skip to main content
SpringerLink
Log in

Cell Therapy for Epilepsy

  • Chapter
  • First Online:
Cell Therapy

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

  • 1249 Accesses

Abstract

Epilepsy is one of the most common chronic neurological conditions that affects about 1% of the world population. One third of the epilepsies are refractory to medical treatment, and, therefore, it is important to search for alternative treatments. One of these alternative approaches could be cell therapy. In this chapter, we provide an overview of the results obtained by the direct grafting of cells in various animal models of drug-resistant epilepsy and discuss the potential of this approach and the issues that remain to be addressed before attempting translation in humans. In addition, we discuss a new cell therapy approach based on the encapsulated cell biodelivery (ECB) system and introduce preliminary data from our laboratory.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Reynolds EH, Kinnier Wilson JV. Psychoses of epilepsy in Babylon: the oldest account of the disorder. Epilepsia. 2008;49(9):1488–90. doi:10.1111/j.1528-1167.2008.01614.x.

    Article  PubMed  Google Scholar 

  2. Zanchin G. Considerations on “the sacred disease” by Hippocrates. J Hist Neurosci. 1992;1(2):91–5. doi:10.1080/09647049209525520.

    Article  CAS  PubMed  Google Scholar 

  3. Fisher RS. Commentary: operational definition of epilepsy survey. Epilepsia. 2014;55(11):1688. doi:10.1111/epi.12829.

    Article  PubMed  Google Scholar 

  4. Sridharan R. Epidemiology of epilepsy. Curr Sci India. 2002;82(6):664–70.

    Google Scholar 

  5. Stephen LJ, Brodie MJ. Epilepsy in elderly people. Lancet. 2000;355(9213):1441–6. doi:10.1016/S0140-6736(00)02149-8.

    Article  CAS  PubMed  Google Scholar 

  6. TL B, WJ B. Pathological findings in epilepsy. Surgical treatment of the epilepsies. New York: Raven Press; 1987.

    Google Scholar 

  7. Turski WA, Cavalheiro EA, Schwarz M, Czuczwar SJ, Kleinrok Z, Turski L. Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study. Behav Brain Res. 1983;9(3):315–35.

    Article  CAS  PubMed  Google Scholar 

  8. Biagini G, Baldelli E, Longo D, Pradelli L, Zini I, Rogawski MA, et al. Endogenous neurosteroids modulate epileptogenesis in a model of temporal lobe epilepsy. Exp Neurol. 2006;201(2):519–24. doi:10.1016/j.expneurol.2006.04.029.

    Article  CAS  PubMed  Google Scholar 

  9. Pitkanen A, Sutula TP. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol. 2002;1(3):173–81.

    Article  PubMed  Google Scholar 

  10. Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C, Turski L. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia. 1991;32(6):778–82.

    Article  CAS  PubMed  Google Scholar 

  11. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342(5):314–9. doi:10.1056/NEJM200002033420503.

    Article  CAS  PubMed  Google Scholar 

  12. Pitkanen A, Lukasiuk K. Mechanisms of epileptogenesis and potential treatment targets. Lancet Neurol. 2011;10(2):173–86. doi:10.1016/S1474-4422(10)70310-0.

    Article  PubMed  Google Scholar 

  13. Stafstrom CE. Epilepsy comorbidities: how can animal models help? Adv Exp Med Biol. 2014;813:273–81. doi:10.1007/978-94-017-8914-1_22.

    Article  PubMed  Google Scholar 

  14. Shetty AK, Upadhya D. GABA-ergic cell therapy for epilepsy: advances, limitations and challenges. Neurosci Biobehav Rev. 2016;62:35–47. doi:10.1016/j.neubiorev.2015.12.014.

    Article  CAS  PubMed  Google Scholar 

  15. Gage FH. Mammalian neural stem cells. Science. 2000;287(5457):1433–8.

    Article  CAS  PubMed  Google Scholar 

  16. Shetty AK, Zaman V, Hattiangady B. Repair of the injured adult hippocampus through graft-mediated modulation of the plasticity of the dentate gyrus in a rat model of temporal lobe epilepsy. J Neurosci. 2005;25(37):8391–401. doi:10.1523/JNEUROSCI.1538-05.2005.

    Article  CAS  PubMed  Google Scholar 

  17. Ruschenschmidt C, Koch PG, Brustle O, Beck H. Functional properties of ES cell-derived neurons engrafted into the hippocampus of adult normal and chronically epileptic rats. Epilepsia. 2005;46(Suppl 5):174–83. doi:10.1111/j.1528-1167.2005.01028.x.

    Article  PubMed  Google Scholar 

  18. Carpentino JE, Hartman NW, Grabel LB, Naegele JR. Region-specific differentiation of embryonic stem cell-derived neural progenitor transplants into the adult mouse hippocampus following seizures. J Neurosci Res. 2008;86(3):512–24. doi:10.1002/jnr.21514.

    Article  CAS  PubMed  Google Scholar 

  19. Shetty AK, Hattiangady B. Concise review: prospects of stem cell therapy for temporal lobe epilepsy. Stem Cells. 2007;25(10):2396–407. doi:10.1634/stemcells.2007-0313.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Costa-Ferro ZS, Souza BS, Leal MM, Kaneto CM, Azevedo CM, da Silva IC, et al. Transplantation of bone marrow mononuclear cells decreases seizure incidence, mitigates neuronal loss and modulates pro-inflammatory cytokine production in epileptic rats. Neurobiol Dis. 2012;46(2):302–13. doi:10.1016/j.nbd.2011.12.001.

    Article  CAS  PubMed  Google Scholar 

  21. Palma E, Roseti C, Maiolino F, Fucile S, Martinello K, Mazzuferi M, et al. GABA(A)-current rundown of temporal lobe epilepsy is associated with repetitive activation of GABA(A) “phasic” receptors. Proc Natl Acad Sci U S A. 2007;104(52):20944–8. doi:10.1073/pnas.0710522105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Soukupova M, Binaschi A, Falcicchia C, Zucchini S, Roncon P, Palma E, et al. Impairment of GABA release in the hippocampus at the time of the first spontaneous seizure in the pilocarpine model of temporal lobe epilepsy. Exp Neurol. 2014;257:39–49. doi:10.1016/j.expneurol.2014.04.014.

    Article  CAS  PubMed  Google Scholar 

  23. Hattiangady B, Rao MS, Shetty AK. Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy. Exp Neurol. 2008;212(2):468–81. doi:10.1016/j.expneurol.2008.04.040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Baraban SC, Southwell DG, Estrada RC, Jones DL, Sebe JY, Alfaro-Cervello C, et al. Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice. Proc Natl Acad Sci U S A. 2009;106(36):15472–7. doi:10.1073/pnas.0900141106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gallego JM, Sancho FJ, Vidueira S, Ortiz L, Gomez-Pinedo U, Barcia JA. Injection of embryonic median ganglionic eminence cells or fibroblasts within the amygdala in rats kindled from the piriform cortex. Seizure. 2010;19(8):461–6. doi:10.1016/j.seizure.2010.06.001.

    Article  PubMed  Google Scholar 

  26. De la Cruz E, Zhao M, Guo L, Ma H, Anderson SA, Schwartz TH. Interneuron progenitors attenuate the power of acute focal ictal discharges. Neurotherapeutics. 2011;8(4):763–73. doi:10.1007/s13311-011-0058-9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Roper SN, Steindler DA. Stem cells as a potential therapy for epilepsy. Exp Neurol. 2013;244:59–66. doi:10.1016/j.expneurol.2012.01.004.

    Article  CAS  PubMed  Google Scholar 

  28. Long Q, Qiu B, Wang K, Yang J, Jia C, Xin W, et al. Genetically engineered bone marrow mesenchymal stem cells improve functional outcome in a rat model of epilepsy. Brain Res. 2013;1532:1–13. doi:10.1016/j.brainres.2013.07.020.

    Article  CAS  PubMed  Google Scholar 

  29. Emerich DF, Orive G, Thanos C, Tornoe J, Wahlberg LU. Encapsulated cell therapy for neurodegenerative diseases: from promise to product. Adv Drug Deliv Rev. 2014;67–68:131–41. doi:10.1016/j.addr.2013.07.008.

    Article  PubMed  Google Scholar 

  30. Lindvall O, Wahlberg LU. Encapsulated cell biodelivery of GDNF: a novel clinical strategy for neuroprotection and neuroregeneration in Parkinson’s disease? Exp Neurol. 2008;209(1):82–8. doi:10.1016/j.expneurol.2007.08.019.

    Article  CAS  PubMed  Google Scholar 

  31. Nikitidou L, Torp M, Fjord-Larsen L, Kusk P, Wahlberg LU, Kokaia M. Encapsulated galanin-producing cells attenuate focal epileptic seizures in the hippocampus. Epilepsia. 2014;55(1):167–74. doi:10.1111/epi.12470.

    Article  CAS  PubMed  Google Scholar 

  32. Tatemoto K, Rokaeus A, Jornvall H, McDonald TJ, Mutt V. Galanin—a novel biologically active peptide from porcine intestine. FEBS Lett. 1983;164(1):124–8.

    Article  CAS  PubMed  Google Scholar 

  33. Kuteeva E, Wardi T, Lundstrom L, Sollenberg U, Langel U, Hokfelt T, et al. Differential role of galanin receptors in the regulation of depression-like behavior and monoamine/stress-related genes at the cell body level. Neuropsychopharmacology. 2008;33(11):2573–85. doi:10.1038/sj.npp.1301660.

    Article  CAS  PubMed  Google Scholar 

  34. Counts SE, He B, Che S, Ginsberg SD, Mufson EJ. Galanin fiber hyperinnervation preserves neuroprotective gene expression in cholinergic basal forebrain neurons in Alzheimer's disease. J Alzheimer's Dis. 2009;18(4):885–96. doi:10.3233/JAD-2009-1196.

    Article  CAS  Google Scholar 

  35. Kokaia M, Holmberg K, Nanobashvili A, ZQ X, Kokaia Z, Lendahl U, et al. Suppressed kindling epileptogenesis in mice with ectopic overexpression of galanin. Proc Natl Acad Sci U S A. 2001;98(24):14006–11. doi:10.1073/pnas.231496298.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lerner JT, Sankar R, Mazarati AM. Galanin and epilepsy. Cell Mol Life Sci. 2008;65(12):1864–71. doi:10.1007/s00018-008-8161-8.

    Article  CAS  PubMed  Google Scholar 

  37. Paradiso B, Zucchini S, Su T, Bovolenta R, Berto E, Marconi P, et al. Localized overexpression of FGF-2 and BDNF in hippocampus reduces mossy fiber sprouting and spontaneous seizures up to 4 weeks after pilocarpine-induced status epilepticus. Epilepsia. 2011;52(3):572–8. doi:10.1111/j.1528-1167.2010.02930.x.

    Article  PubMed  Google Scholar 

  38. Simonato M, Tongiorgi E, Kokaia M. Angels and demons: neurotrophic factors and epilepsy. Trends Pharmacol Sci. 2006;27(12):631–8. doi:10.1016/j.tips.2006.10.002.

    Article  CAS  PubMed  Google Scholar 

  39. Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors. 2004;22(3):123–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cohen-Cory S, Kidane AH, Shirkey NJ, Marshak S. Brain-derived neurotrophic factor and the development of structural neuronal connectivity. Dev Neurobiol. 2010;70(5):271–88. doi:10.1002/dneu.20774.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Yoshii A, Constantine-Paton M. Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 2010;70(5):304–22. doi:10.1002/dneu.20765.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Kuramoto S, Yasuhara T, Agari T, Kondo A, Jing M, Kikuchi Y, et al. BDNF-secreting capsule exerts neuroprotective effects on epilepsy model of rats. Brain Res. 2011;1368:281–9. doi:10.1016/j.brainres.2010.10.054.

    Article  CAS  PubMed  Google Scholar 

  43. Koyama R, Ikegaya Y. To BDNF or not to BDNF: that is the epileptic hippocampus. Neuroscientist. 2005;11(4):282–7. doi:10.1177/1073858405278266.

    Article  CAS  PubMed  Google Scholar 

  44. Larmet Y, Reibel S, Carnahan J, Nawa H, Marescaux C, Depaulis A. Protective effects of brain-derived neurotrophic factor on the development of hippocampal kindling in the rat. Neuroreport. 1995;6(14):1937–41.

    Article  CAS  PubMed  Google Scholar 

  45. Palma E, Torchia G, Limatola C, Trettel F, Arcella A, Cantore G, et al. BDNF modulates GABAA receptors microtransplanted from the human epileptic brain to Xenopus oocytes. Proc Natl Acad Sci U S A. 2005;102(5):1667–72. doi:10.1073/pnas.0409442102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Airaksinen MS, Saarma M. The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci. 2002;3(5):383–94. doi:10.1038/nrn812.

    Article  CAS  PubMed  Google Scholar 

  47. Paratcha G, Ledda F, Ibanez CF. The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell. 2003;113(7):867–79.

    Article  CAS  PubMed  Google Scholar 

  48. Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science. 1993;260(5111):1130–2.

    Article  CAS  PubMed  Google Scholar 

  49. Kokaia M, Lindvall O. The GDNF family of neurotrophic factors and epilepsy. New York: Nova Science Publishers; 2005.

    Google Scholar 

  50. Tornoe J, Torp M, Jorgensen JR, Emerich DF, Thanos C, Bintz B, et al. Encapsulated cell-based biodelivery of meteorin is neuroprotective in the quinolinic acid rat model of neurodegenerative disease. Restor Neurol Neurosci. 2012;30(3):225–36. doi:10.3233/RNN-2012-110199.

    CAS  PubMed  Google Scholar 

  51. Eriksdotter-Jonhagen M, Linderoth B, Lind G, Aladellie L, Almkvist O, Andreasen N, et al. Encapsulated cell biodelivery of nerve growth factor to the Basal forebrain in patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2012;33(1):18–28. doi:10.1159/000336051.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Sciences, University of Ferrara, via Fossato di Mortara 17-19, Ferrara, Italy

    Chiara Falcicchia Ph.D., Giovanna Paolone Ph.D. & Michele Simonato M.D.

Authors
  1. Chiara Falcicchia Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanna Paolone Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michele Simonato M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michele Simonato M.D. .

Editor information

Editors and Affiliations

  1. NsGene, Inc., Providence, Rhode Island, USA

    Dwaine F. Emerich

  2. Paseo de la Universidad 7, Vitoria-Gasteiz, Spain

    Gorka Orive

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Falcicchia, C., Paolone, G., Simonato, M. (2017). Cell Therapy for Epilepsy. In: Emerich, D., Orive, G. (eds) Cell Therapy. Molecular and Translational Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-57153-9_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-57153-9_5

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-57152-2

  • Online ISBN: 978-3-319-57153-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation