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Combination of Nanomaterials and Mesenchymal Stem Cells for Effective Treatment of Epilepsy

Nasera Rizwana


Around 50 million people across the world are affected due to epilepsy. One of the most common symptoms of epilepsy is seizures which is usually controlled by administering anti-epileptic drugs. But these drugs fail to control seizures for a long period of time as they do not change the underlying physiological conditions of the brain. Therefore, it is very important to alter the biological mechanism that causes seizures. This can be done with the advancements made in regenerative medicine. Stem cells have shown promising results when used for neurodegenerative diseases. Cell survival, proliferation, and differentiation are difficult to monitor when used to treat epilepsy. To overcome these problems, nanoparticles have been used. It is known that nanoparticles can easily cross the blood-brain barrier and also help in the growth and differentiation of stem cells. In this review, we aim to discuss the use of nanomaterials in conjunction with mesenchymal stem cells for the treatment of epilepsy.   


Mesenchymal stem cells (MSCs), Nanomaterials, Epilepsy, Anti-Epileptic drugs (AEDs), Seizures

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Banerjee PN, Filippi D, Allen Hauser W. The descriptive epidemiology of epilepsy-a review. Epilepsy Res. 2009 Jul;85(1):31–45.

Owen A, Pirmohamed M, Tettey JN, Morgan P, Chadwick D, Park BK. Carbamazepine is not a substrate for P-glycoprotein. Br J Clin Pharmacol. 2001 Apr;51(4):345–9.

Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314–9.

Schmidt D, Löscher W. New developments in antiepileptic drug resistance: an integrative view. Epilepsy Curr. 2009 Apr;9(2):47–52.

Tennison M, Greenwood R, Lewis D, Thorn M. Discontinuing antiepileptic drugs in children with epilepsy. A comparison of a six-week and a nine-month taper period. N Engl J Med. 1994 May 19;330(20):1407–10.

Perucca, E. Clinical pharmacology and therapeutic use of the new antiepileptic drugs. Fundamental & Clinical Pharmacology. 2001;15:405–17.

Löscher W, Gernert M, Heinemann U. Cell and gene therapies in epilepsy-Promising avenues or blind alleys? Trends in neurosciences. 2008 Mar 1;31:62–73.

Shetty AK. Hippocampal Injury Induced Cognitive and Mood Dysfunction, Altered Neurogenesis and Epilepsy: Can Early Neural Stem Cell Grafting Intervention Provide Protection? Epilepsy Behav. 2014 Sep;38:117–24.

Agadi S, Shetty AK. Concise Review: Prospects of Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells for Treating Status Epilepticus and Chronic Epilepsy. Stem Cells. 2015 Jul;33(7):2093–103.

Forostyak S, Homola A, Turnovcova K, Svitil P, Jendelova P, Sykova E. Intrathecal delivery of mesenchymal stromal cells protects the structure of altered perineuronal nets in SOD1 rats and amends the course of ALS. Stem Cells. 2014 Dec;32(12):3163–72.

Maisano X, Litvina E, Tagliatela S, Aaron GB, Grabel LB, Naegele JR. Differentiation and functional incorporation of embryonic stem cell-derived GABAergic interneurons in the dentate gyrus of mice with temporal lobe epilepsy. J Neurosci. 2012 Jan 4;32(1):46–61.

Kwon M-S, Noh M-Y, Oh K-W, Cho K-A, Kang B-Y, Kim K-S, et al. The immunomodulatory effects of human mesenchymal stem cells on peripheral blood mononuclear cells in ALS patients. J Neurochem. 2014 Oct;131(2):206–18.

Hlebokazov F, Dakukina T, Ihnatsenko S, Kosmacheva S, Potapnev M, Shakhbazau A, et al. Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study. Adv Med Sci. 2017 Sep;62(2):273–9.

Milczarek O, Jarocha D, Starowicz-Filip A, Kwiatkowski S, Badyra B, Majka M. Multiple Autologous Bone Marrow-Derived CD271+ Mesenchymal Stem Cell Transplantation Overcomes Drug-Resistant Epilepsy in Children. Stem Cells Transl Med. 2018 Jan;7(1):20–33.

Mareschi K, Novara M, Rustichelli D, Ferrero I, Guido D, Carbone E, et al. Neural differentiation of human mesenchymal stem cells: Evidence for expression of neural markers and eag K+ channel types. Exp Hematol. 2006 Nov;34(11):1563–72.

Perucca E. An Introduction to Antiepileptic Drugs. Epilepsia. 2005;46(s4):31–7.

Pellock JM. Carbamazepine side effects in children and adults. Epilepsia. 1987;28 Suppl 3:S64-70.

Aw W, Mj M. Limitation by gabapentin of high frequency action potential firing by mouse central neurons in cell culture. Epilepsy Res. 1994;17(1):1–11.

Kocsis JD, Honmou O. Gabapentin increases GABA-induced depolarization in rat neonatal optic nerve. Neurosci Lett. 1994 Mar 14;169(1–2):181–4.

Cheung H, Kamp D, Harris E. An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels. Epilepsy Res. 1992 Nov;13(2):107–12.

Brodie MJ. Lamotrigine. Lancet. 1992 Jun 6;339(8806):1397–400.

Rogawski MA. Diverse mechanisms of antiepileptic drugs in the development pipeline. Epilepsy Res. 2006 Jun;69(3):273–94.

Petroff OA, Rothman DL, Behar KL, Mattson RH. Initial observations on effect of vigabatrin on in vivo 1H spectroscopic measurements of gamma-aminobutyric acid, glutamate, and glutamine in human brain. Epilepsia. 1995 May;36(5):457–64.

French JA, Mosier M, Walker S, Sommerville K, Sussman N. A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Vigabatrin Protocol 024 Investigative Cohort. Neurology. 1996 Jan;46(1):54–61.

White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH. Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Research. 1997;28(3):167–79.

Rogawski MA, Porter RJ. Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev. 1990 Sep;42(3):223–86.

Nielsen EB, Suzdak PD, Andersen KE, Knutsen LJ, Sonnewald U, Braestrup C. Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor. Eur J Pharmacol. 1991 Apr 24;196(3):257–66.

Hamandi K, Sander JW. Pregabalin: a new antiepileptic drug for refractory epilepsy. Seizure. 2006 Mar;15(2):73–8.

Ojemann LM, Ojemann GA, Dodrill CB, Crawford CA, Holmes MD, Dudley DL. Language Disturbances as Side Effects of Topiramate and Zonisamide Therapy. Epilepsy Behav. 2001 Dec;2(6):579–84.

Haefely W, Kulcsár A, Möhler H, Pieri L, Polc P, Schaffner R. Possible involvement of GABA in the central actions of benzodiazepines. Adv Biochem Psychopharmacol. 1975;(14):131–51.

Robertson MM. Current status of the 1,4- and 1,5-benzodiazepines in the treatment of epilepsy: the place of clobazam. Epilepsia. 1986;27 Suppl 1:S27-41.

Riss J, Cloyd J, Gates J, Collins S. Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69–86.

Rho JM, Donevan SD, Rogawski MA. Mechanism of action of the anticonvulsant felbamate: opposing effects on N-methyl-D-aspartate and gamma-aminobutyric acidA receptors. Ann Neurol. 1994 Feb;35(2):229–34.

Ren G, Chen X, Dong F, Li W, Ren X, Zhang Y, et al. Concise review: mesenchymal stem cells and translational medicine: emerging issues. Stem Cells Transl Med. 2012 Jan;1(1):51–8.

Yonemori K, Tsuta K, Ono M, Shimizu C, Hirakawa A, Hasegawa T, et al. Disruption of the blood brain barrier by brain metastases of triple-negative and basal-type breast cancer but not HER2/neupositive breast cancer. Cancer. 2010 Jan 15;116(2):302–8.

Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH. The nanosilica hazard: another variable entity. Particle and Fibre Toxicology. 2010;7(1):39.

Faustino C, Rijo P, Reis CP. Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer’s disease. Pharmacol Res. 2017 Jun;120:68–87.

Green JJ, Zhou BY, Mitalipova MM, Beard C, Langer R, Jaenisch R, et al. Nanoparticles for gene transfer to human embryonic stem cell colonies. Nano Lett. 2008 Oct;8(10):3126–30.

Dvir T, Timko BP, Kohane DS, Langer R. Nanotechnological strategies for engineering complex tissues. Nat Nanotechnol. 2011 Jan;6(1):13–22.

Dayem AA, Kim B, Gurunathan S, Choi HY, Yang G, Saha SK, et al. Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathways. Biotechnol J. 2014 Jul;9(7):934–43.

Patel T, Zhou J, Piepmeier JM, Saltzman WM. Polymeric Nanoparticles for Drug Delivery to the Central Nervous System. Adv Drug Deliv Rev. 2012;64(7):701–5.

Pardeshi CV, Belgamwar VS. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: an excellent platform for brain targeting. Expert Opin Drug Deliv. 2013 Jul;10(7):957–72.

Lu Y, Jeong Y-T, Li X, Kim MJ, Park P-H, Hwang S-L, et al. Emodin Isolated from Polygoni cuspidati Radix Inhibits TNF-α and IL-6 Release by Blockading NF-κB and MAP Kinase Pathways in Mast Cells Stimulated with PMA Plus A23187. Biomol Ther (Seoul). 2013 Nov;21(6):435–41.

Xie J, Shen Z, Anraku Y, Kataoka K, Chen X. Nanomaterial-based blood-brain-barrier (BBB) crossing strategies. Biomaterials. 2019 Dec;224:119491.

Li J, Feng L, Fan L, Zha Y, Guo L, Zhang Q, et al. Targeting the brain with PEG-PLGA nanoparticles modified with phage-displayed peptides. Biomaterials. 2011 Jul;32(21):4943–50.

Batrakova EV, Gendelman HE, Kabanov AV. Cell-mediated drug delivery. Expert Opin Drug Deliv. 2011 Apr;8(4):415–33.

Das K, Madhusoodan AP, Mili B, Kumar A, Saxena AC, Kumar K, et al. Functionalized carbon nanotubes as suitable scaffold materials for proliferation and differentiation of canine mesenchymal stem cells. Int J Nanomedicine. 2017;12:3235–52.

Tasnim N, Thakur V, Chattopadhyay M, Joddar B. The Efficacy of Graphene Foams for Culturing Mesenchymal Stem Cells and Their Differentiation into Dopaminergic Neurons. Stem Cells Int. 2018;2018:3410168.

Kenry null, Lee WC, Loh KP, Lim CT. When stem cells meet graphene: Opportunities and challenges in regenerative medicine. Biomaterials. 2018 Feb;155:236–50.

Guo W, Qiu J, Liu J, Liu H. Graphene microfiber as a scaffold for regulation of neural stem cells differentiation. Scientific Reports. 2017;7(1):5678.

Teleanu DM, Chircov C, Grumezescu AM, Teleanu RI. Neurotoxicity of Nanomaterials: An Upto-Date Overview. Nanomaterials (Basel). 2019;9(1).

Conti E, Gregori M, Radice I, Da Re F, Grana D, Re F, et al. Multifunctional liposomes interact with Abeta in human biological fluids: Therapeutic implications for Alzheimer’s disease. Neurochem Int. 2017 Sep;108:60–5.

Zheng M, Ruan S, Liu S, Sun T, Qu D, Zhao H, et al. Self-Targeting Fluorescent Carbon Dots for Diagnosis of Brain Cancer Cells. ACS Nano. 2015;9(11):11455–61.

Li X, Zhao Y, Cheng S, Han S, Shu M, Chen B, et al. Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair. Biomaterials. 2017 Aug;137:73–86.

Yan F, Li M, Zhang H-Q, Li G-L, Hua Y, Shen Y, et al. Collagen-chitosan scaffold impregnated with bone marrow mesenchymal stem cells for treatment of traumatic brain injury. Neural Regen Res. 2019 Oct;14(10):1780–6.

Menei P, Pean JM, Nerrière-Daguin V, Jollivet C, Brachet P, Benoit JP. Intracerebral Implantation of NGF-Releasing Biodegradable Microspheres Protects Striatum against Excitotoxic Damage. Experimental Neurology. 2000;161(1):259–72.

Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater. 2012 Mar 22;24(12):1504–34.

Solanki A, Shah S, Yin PT, Lee K-B. Nanotopography-mediated Reverse Uptake for siRNA Delivery into Neural Stem Cells to Enhance Neuronal Differentiation. Scientific Reports. 2013;3(1):1553.

Saito N, Usui Y, Aoki K, Narita N, Shimizu M, Hara K, et al. Carbon nanotubes: biomaterial applications. Chem Soc Rev. 2009;38(7):1897–903.

Salama-Cohen P, Arévalo M-A, Grantyn R, Rodríguez-Tébar A. Notch and NGF/p75NTR control dendrite morphology and the balance of excitatory/inhibitory synaptic input to hippocampal neurones through Neurogenin 3. J Neurochem. 2006 Jun;97(5):1269–78.

Chen Y-S, Hsiue G-H. Directing neural differentiation of mesenchymal stem cells by carboxylated multiwalled carbon nanotubes. Biomaterials. 2013 Jul;34(21):4936–44.

Park SY, Kang B-S, Hong S. Improved neural differentiation of human mesenchymal stem cells interfaced with carbon nanotube scaffolds. Nanomedicine (Lond). 2013 May;8(5):715–23.

Kim JA, Jang EY, Kang TJ, Yoon S, Ovalle-Robles R, Rhee WJ, et al. Regulation of morphogenesis and neural differentiation of human mesenchymal stem cells using carbon nanotube sheets. Integr Biol (Camb). 2012 Jun;4(6):587–94.

Lee JH, Lee J-Y, Yang SH, Lee E-J, Kim H-W. Carbon nanotube-collagen three-dimensional culture of mesenchymal stem cells promotes expression of neural phenotypes and secretion of neurotrophic factors. Acta Biomater. 2014 Oct;10(10):4425–36.

Asgari V, Landarani-Isfahani A, Salehi H, Amirpour N, Hashemibeni B, Kazemi M, et al. Direct Conjugation of Retinoic Acid with Gold Nanoparticles to Improve Neural Differentiation of Human Adipose Stem Cells. J Mol Neurosci. 2020;70(11):1836–50.

Kim HJ, Lee JS, Park JM, Lee S, Hong SJ, Park JS, et al. Fabrication of Nanocomposites Complexed with Gold Nanoparticles on Polyaniline and Application to Their Nerve Regeneration. ACS Appl Mater Interfaces. 2020;12(27):30750–60.

Xu C, Xu Y, Yang M, Chang Y, Nie A, Liu Z, et al. Black-Phosphorus-Incorporated Hydrogel as a Conductive and Biodegradable Platform for Enhancement of the Neural Differentiation of Mesenchymal Stem Cells. Advanced Functional Materials. 2020;30(39):2000177.

Jedari B, Rahmani A, Naderi M, Nadri S. MicroRNA-7 promotes neural differentiation of trabecular meshwork mesenchymal stem cell on nanofibrous scaffold. J Cell Biochem. 2020 Apr;121(4):2818–27



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