426
Views
38
CrossRef citations to date
0
Altmetric
Review

Engineered BDNF producing cells as a potential treatment for neurologic disease

, , , , &
Pages 1025-1033 | Received 04 Mar 2016, Accepted 25 Apr 2016, Published online: 21 May 2016

References

  • Cohen S, Levi-Montalcini R, Hamburger V. A nerve growth-stimulating factor isolated from SARCOM as 37 and 180. Proc Natl Acad Sci U S A. 1954 Oct;40(10):1014–1018.
  • Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO J. 1982;1(5):549–553.
  • Maisonpierre PC, Belluscio L, Squinto S, et al. Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990 Mar 23;247(4949 Pt 1):1446–1451.
  • Berkemeier LR, Winslow JW, Kaplan DR, et al. Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991 Nov;7(5):857–866. doi:10.1016/0896-6273(91)90287-A.
  • Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000 Jun;10(3):381–391. doi:10.1016/S0959-4388(00)00092-1.
  • Corbit KC, Foster DA, Rosner MR. Protein kinase Cdelta mediates neurogenic but not mitogenic activation of mitogen-activated protein kinase in neuronal cells. Mol Cell Biol. 1999 Jun;19(6):4209–4218. doi:10.1128/MCB.19.6.4209.
  • Dimitropoulou A, Bixby JL. Regulation of retinal neurite growth by alterations in MAPK/ERK kinase (MEK) activity. Brain Res. 2000 Mar 6;858(1):205–214.
  • Bramham CR, Messaoudi E. BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog Neurobiol. 2005 Jun;76(2):99–125. doi:10.1016/j.pneurobio.2005.06.003.
  • Lu B, Nagappan G, Guan X, et al. BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases. Nat Rev Neurosci. 2013 Jun;14(6):401–416. doi:10.1038/nrn3505.
  • Arancibia S, Silhol M, Moulière F, et al. Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis. 2008 Sep;31(3):316–326. doi:10.1016/j.nbd.2008.05.012.
  • Causing CG, Gloster A, Aloyz R, et al. Synaptic innervation density is regulated by neuron-derived BDNF. Neuron. 1997 Feb;18(2):257–267. doi:10.1016/S0896-6273(00)80266-4.
  • Pollock K, Dahlenburg H, Nelson H, et al. Human mesenchymal stem cells genetically engineered to overexpress brain-derived neurotrophic factor improve outcomes in Huntington’s disease mouse models. Mol Ther J Am Soc Gene Ther. 2016 Jan 14. doi:10.1038/mt.2016.12.
  • Adachi N, Numakawa T, Richards M, et al. New insight in expression, transport, and secretion of brain-derived neurotrophic factor: implications in brain-related diseases. World J Biol Chem. 2014 Nov 26;5(4):409–428.
  • Huang EJ, Reichardt LF. Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem. 2003;72:609–642. doi:10.1146/annurev.biochem.72.121801.161629.
  • Woo NH, Teng HK, Siao C-J, et al. Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci. 2005 Aug;8(8):1069–1077. doi:10.1038/nn1510.
  • Pruunsild P, Kazantseva A, Aid T, et al. Dissecting the human BDNF locus: bidirectional transcription, complex splicing, and multiple promoters. Genomics. 2007 Sep;90(3):397–406. doi:10.1016/j.ygeno.2007.05.004.
  • Yan Q, Rosenfeld RD, Matheson CR, et al. Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system. Neuroscience. 1997 May;78(2):431–448. doi:10.1016/S0306-4522(96)00613-6.
  • Timmusk T, Palm K, Metsis M, et al. Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron. 1993 Mar;10(3):475–489. doi:10.1016/0896-6273(93)90335-O.
  • An JJ, Gharami K, Liao G-Y, et al. Distinct role of long 3ʹ UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell. 2008 Jul 11;134(1):175–187.
  • Hong EJ, McCord AE, Greenberg ME. A biological function for the neuronal activity-dependent component of Bdnf transcription in the development of cortical inhibition. Neuron. 2008 Nov 26;60(4):610–624.
  • Chen WG, West AE, Tao X, et al. Upstream stimulatory factors are mediators of Ca2+-responsive transcription in neurons. J Neurosci Off J Soc Neurosci. 2003 Apr 1;23(7):2572–2581.
  • Zafra F, Lindholm D, Castrén E, et al. Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes. J Neurosci Off J Soc Neurosci. 1992 Dec;12(12):4793–4799.
  • Zheng F, Zhou X, Moon C, et al. Regulation of brain-derived neurotrophic factor expression in neurons. Int J Physiol Pathophysiol Pharmacol. 2012;4(4):188–200.
  • Seidah NG, Benjannet S, Pareek S, et al. Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases. Biochem J. 1996 Mar 15;314(Pt 3):951–960.
  • Lee R, Kermani P, Teng KK, et al. Regulation of cell survival by secreted proneurotrophins. Science. 2001 Nov 30;294(5548):1945–1948.
  • Egan MF, Kojima M, Callicott JH, et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257–269.
  • Pezawas L, Verchinski BA, Mattay VS, et al. The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci Off J Soc Neurosci. 2004 Nov 10;24(45):10099–10102.
  • Kleim JA, Chan S, Pringle E, et al. BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat Neurosci. 2006 Jun;9(6):735–737. doi:10.1038/nn1699.
  • Lessmann V, Brigadski T. Mechanisms, locations, and kinetics of synaptic BDNF secretion: an update. Neurosci Res. 2009 Sep;65(1):11–22. doi:10.1016/j.neures.2009.06.004.
  • Gauthier LR, Charrin BC, Borrell-Pagès M, et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell. 2004 Jul 9;118(1):127–138.
  • Cattaneo E, Zuccato C, Tartari M. Normal huntingtin function: an alternative approach to Huntington’s disease. Nat Rev Neurosci. 2005 Dec;6(12):919–930. doi:10.1038/nrn1806.
  • Zuccato C, Tartari M, Crotti A, et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet. 2003 Sep;35(1):76–83. doi:10.1038/ng1250.
  • Zuccato C, Belyaev N, Conforti P, et al. Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington’s disease. J Neurosci Off J Soc Neurosci. 2007 Jun 27;27(26):6972–6983.
  • Soldati C, Bithell A, Johnston C, et al. Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington’s disease. J Neurochem. 2013 Feb;124(3):418–430. doi:10.1111/jnc.12090.
  • Cheng P-L, Song A-H, Wong Y-H, et al. Self-amplifying autocrine actions of BDNF in axon development. Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18430–18435.
  • Cohen-Cory S, Fraser SE. Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo. Nature. 1995 Nov 9;378(6553):192–196.
  • Wirth MJ, Brun A, Grabert J, et al. Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5. Dev Camb Engl. 2003 Dec;130(23):5827–5838.
  • Luikart BW, Nef S, Virmani T, et al. TrkB has a cell-autonomous role in the establishment of hippocampal Schaffer collateral synapses. J Neurosci Off J Soc Neurosci. 2005 Apr 13;25(15):3774–3786.
  • Lush ME, Ma L, Parada LF. TrkB signaling regulates the developmental maturation of the somatosensory cortex. Int J Dev Neurosci Off J Int Soc Dev Neurosci. 2005 Oct;23(6):523–536. doi:10.1016/j.ijdevneu.2005.04.003.
  • Tyler WJ, Pozzo-Miller LD. BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses. J Neurosci Off J Soc Neurosci. 2001 Jun 15;21(12):4249–4258.
  • Tyler WJ, Zhang X, Hartman K, et al. BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses. J Physiol. 2006 Aug 1;574(Pt 3):787–803.
  • Kang H, Schuman EM. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science. 1995 Mar 17;267(5204):1658–1662.
  • Carmignoto G, Pizzorusso T, Tia S, et al. Brain-derived neurotrophic factor and nerve growth factor potentiate excitatory synaptic transmission in the rat visual cortex. J Physiol. 1997 Jan 1;498(Pt 1):153–164.
  • Carvalho AL, Caldeira MV, Santos SD, et al. Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br J Pharmacol. 2008 Mar;153 Suppl 1:S310–24. doi:10.1038/bjp.2008.22.
  • Scharfman HE. Brain-derived neurotrophic factor and epilepsy–a missing link? Epilepsy Curr Am Epilepsy Soc. 2005 Jun;5(3):83–88. doi:10.1111/j.1535-7511.2005.05312.x.
  • Humpel C, Wetmore C, Olson L. Regulation of brain-derived neurotrophic factor messenger RNA and protein at the cellular level in pentylenetetrazol-induced epileptic seizures. Neuroscience. 1993 Apr;53(4):909–918. doi:10.1016/0306-4522(93)90476-V.
  • Vezzani A, Ravizza T, Moneta D, et al. Brain-derived neurotrophic factor immunoreactivity in the limbic system of rats after acute seizures and during spontaneous convulsions: temporal evolution of changes as compared to neuropeptide Y. Neuroscience. 1999;90(4):1445–1461. doi:10.1016/S0306-4522(98)00553-3.
  • Scharfman HE, Goodman JH, Sollas AL, et al. Spontaneous limbic seizures after intrahippocampal infusion of brain-derived neurotrophic factor. Exp Neurol. 2002 Apr;174(2):201–214. doi:10.1006/exnr.2002.7869.
  • He X-P, Kotloski R, Nef S, et al. Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. Neuron. 2004 Jul 8;43(1):31–42.
  • Siegel GJ, Chauhan NB. Neurotrophic factors in Alzheimer’s and Parkinson’s disease brain. Brain Res Brain Res Rev. 2000 Sep;33(2–3):199–227. doi:10.1016/S0165-0173(00)00030-8.
  • Howells DW, Porritt MJ, Wong JY, et al. Reduced BDNF mRNA expression in the Parkinson’s disease substantia nigra. Exp Neurol. 2000 Nov;166(1):127–135. doi:10.1006/exnr.2000.7483.
  • Takahashi M, Ishikawa K, Sato N, et al. Reduced brain-derived neurotrophic factor (BDNF) mRNA expression and presence of BDNF-immunoreactive granules in the spinocerebellar ataxia type 6 (SCA6) cerebellum. Neuropathol Off J Jpn Soc Neuropathol. 2012 Dec;32(6):595–603. doi:10.1111/j.1440-1789.2012.01302.x.
  • Strand AD, Baquet ZC, Aragaki AK, et al. Expression profiling of Huntington’s disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration. J Neurosci Off J Soc Neurosci. 2007 Oct 24;27(43):11758–11768.
  • Ciammola A, Sassone J, Cannella M, et al. Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington’s disease patients. Am J Med Genet Part B Neuropsychiatr Genet Off Publ Int Soc Psychiatr Genet. 2007 Jun 5;144B(4):574–577.
  • Conforti P, Ramos C, Apostol BL, et al. Blood level of brain-derived neurotrophic factor mRNA is progressively reduced in rodent models of Huntington’s disease: restoration by the neuroprotective compound CEP-1347. Mol Cell Neurosci. 2008 Sep;39(1):1–7. doi:10.1016/j.mcn.2008.04.012.
  • Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev. 2012 Apr;64(2):238–258. doi:10.1124/pr.111.004580.
  • Bergami M, Rimondini R, Santi S, et al. Deletion of TrkB in adult progenitors alters newborn neuron integration into hippocampal circuits and increases anxiety-like behavior. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15570–15575.
  • Chen Z-Y, Jing D, Bath KG, et al. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science. 2006 Oct 6;314(5796):140–143.
  • Zuccato C, Marullo M, Vitali B, et al. Brain-derived neurotrophic factor in patients with Huntington’s disease. PloS One. 2011;6(8):e22966. doi:10.1371/journal.pone.0022966.
  • Spieles-Engemann AL, Steece-Collier K, Behbehani MM, et al. Subthalamic nucleus stimulation increases brain derived neurotrophic factor in the Nigrostriatal system and primary motor cortex. J Park Dis. 2011 May 31;1(1):123–136.
  • Knüsel B, Beck KD, Winslow JW, et al. Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J Neurosci Off J Soc Neurosci. 1992 Nov;12(11):4391–4402.
  • Nagahara AH, Mateling M, Kovacs I, et al. Early BDNF treatment ameliorates cell loss in the entorhinal cortex of APP transgenic mice. J Neurosci Off J Soc Neurosci. 2013 Sep 25;33(39):15596–15602.
  • Nagahara AH, Merrill DA, Coppola G, et al. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med. 2009 Mar;15(3):331–337. doi:10.1038/nm.1912.
  • Tsukahara T, Takeda M, Shimohama S, et al. Effects of brain-derived neurotrophic factor on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys. Neurosurgery. 1995 Oct;37(4):733–9; discussion 739–41.
  • Drew MR, Denny CA, Hen R. Arrest of adult hippocampal neurogenesis in mice impairs single- but not multiple-trial contextual fear conditioning. Behav Neurosci. 2010 Aug;124(4):446–454. doi:10.1037/a0020081.
  • Saxe MD, Battaglia F, Wang J-W, et al. Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17501–17506.
  • Chai H, Wu W, So K-F, et al. Long-term effects of a single dose of brain-derived neurotrophic factor on motoneuron survival following spinal root avulsion in the adult rat. Neurosci Lett. 1999 Oct 29;274(3):147–150.
  • Chiu AY, Chen EW, Loera S. Distinct neurotrophic responses of axotomized motor neurons to BDNF and CNTF in adult rats. Neuroreport. 1994 Feb 24;5(6):693–696.
  • Yan Q, Matheson C, Lopez OT, et al. The biological responses of axotomized adult motoneurons to brain-derived neurotrophic factor. J Neurosci Off J Soc Neurosci. 1994 Sep;14(9):5281–5291.
  • Spires TL, Grote HE, Varshney NK, et al. Environmental enrichment rescues protein deficits in a mouse model of Huntington’s disease, indicating a possible disease mechanism. J Neurosci Off J Soc Neurosci. 2004 Mar 3;24(9):2270–2276.
  • Nitta A, Murai R, Suzuki N, et al. Diabetic neuropathies in brain are induced by deficiency of BDNF. Neurotoxicol Teratol. 2002 Oct;24(5):695–701. doi:10.1016/S0892-0362(02)00220-9.
  • Lever I, Cunningham J, Grist J, et al. Release of BDNF and GABA in the dorsal horn of neuropathic rats. Eur J Neurosci. 2003 Sep;18(5):1169–1174. doi:10.1046/j.1460-9568.2003.02848.x.
  • Eaton MJ, Blits B, Ruitenberg MJ, et al. Amelioration of chronic neuropathic pain after partial nerve injury by adeno-associated viral (AAV) vector-mediated over-expression of BDNF in the rat spinal cord. Gene Ther. 2002 Oct;9(20):1387–1395. doi:10.1038/sj.gt.3301814.
  • Katsu-Jiménez Y, Loria F, Corona JC, et al. Gene transfer of brain derived neurotrophic factor (BDNF) prevents neurodegeneration triggered by frataxin deficiency. Mol Ther J Am Soc Gene Ther. 2016 Feb 5. doi:10.1038/mt.2016.32.
  • Tuszynski MH, Mafong E, Meyer S. Central infusions of brain-derived neurotrophic factor and neurotrophin-4/5, but not nerve growth factor and neurotrophin-3, prevent loss of the cholinergic phenotype in injured adult motor neurons. Neuroscience. 1996 Apr;71(3):761–771. doi:10.1016/0306-4522(95)00440-8.
  • Ochs G, Penn RD, York M, et al. A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Mot Neuron Disord Off Publ World Fed Neurol Res Group Mot Neuron Dis. 2000 Jun;1(3):201–206.
  • The BDNF Study Group. A controlled trial of recombinant methionyl human BDNF in ALS: the BDNF study group (Phase III). Neurology. 1999 Apr 22;52(7):1427–1433.
  • Ankeny DP, McTigue DM, Guan Z, et al. Pegylated brain-derived neurotrophic factor shows improved distribution into the spinal cord and stimulates locomotor activity and morphological changes after injury. Exp Neurol. 2001 Jul;170(1):85–100. doi:10.1006/exnr.2001.7699.
  • Pardridge WM, Wu D, Sakane T. Combined use of carboxyl-directed protein pegylation and vector-mediated blood-brain barrier drug delivery system optimizes brain uptake of brain-derived neurotrophic factor following intravenous administration. Pharm Res. 1998 Apr;15(4):576–582. doi:10.1023/A:1011981927620.
  • Pan W, Banks WA, Fasold MB, et al. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology. 1998 Dec;37(12):1553–1561. doi:10.1016/S0028-3908(98)00141-5.
  • Pardridge WM, Kang YS, Buciak JL. Transport of human recombinant brain-derived neurotrophic factor (BDNF) through the rat blood-brain barrier in vivo using vector-mediated peptide drug delivery. Pharm Res. 1994 May;11(5):738–746.
  • Poduslo JF, Curran GL. Permeability at the blood-brain and blood-nerve barriers of the neurotrophic factors: NGF, CNTF, NT-3, BDNF. Brain Res Mol Brain Res. 1996 Mar;36(2):280–286.
  • Rodriguez-Lebron E, Denovan-Wright EM, Nash K, et al. Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington’s disease transgenic mice. Mol Ther J Am Soc Gene Ther. 2005 Oct;12(4):618–633. doi:10.1016/j.ymthe.2005.05.006.
  • Arregui L, Benítez JA, Razgado LF, et al. Adenoviral astrocyte-specific expression of BDNF in the striata of mice transgenic for Huntington’s disease delays the onset of the motor phenotype. Cell Mol Neurobiol. 2011 Nov;31(8):1229–1243. doi:10.1007/s10571-011-9725-y.
  • Bemelmans A-P, Horellou P, Pradier L, et al. Brain-derived neurotrophic factor-mediated protection of striatal neurons in an excitotoxic rat model of Huntington’s disease, as demonstrated by adenoviral gene transfer. Hum Gene Ther. 1999 Dec 10;10(18):2987–2997.
  • Kells AP, Henry RA, Connor B. AAV-BDNF mediated attenuation of quinolinic acid-induced neuropathology and motor function impairment. Gene Ther. 2008 Jul;15(13):966–977. doi:10.1038/gt.2008.23.
  • Goldberg NS, Caesar J, Park A, et al. Neural stem cells rescue cognitive and motor dysfunction in a transgenic model of dementia with Lewy bodies through a BDNF-dependent mechanism. Stem Cell Rep. 2015 Nov 10;5(5):791–804.
  • Benraiss A, Toner MJ, Xu Q, et al. Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of Huntington’s disease. Cell Stem Cell. 2013 Jun 6;12(6):787–799.
  • Alawdi SH, El-Denshary ES, Safar MM, et al. Neuroprotective effect of nanodiamond in Alzheimer’s disease rat model: a pivotal role for modulating NF-κB and STAT3 signaling. Mol Neurobiol. 2016 Feb 20:1–13. Epub ahead of print.
  • Dey ND, Bombard MC, Roland BP, et al. Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington’s disease. Behav Brain Res. 2010 Dec 25;214(2):193–200.
  • Benraiss A, Bruel-Jungerman E, Lu G, et al. Sustained induction of neuronal addition to the adult rat neostriatum by AAV4-delivered noggin and BDNF. Gene Ther. 2012 May;19(5):483–493. doi:10.1038/gt.2011.114.
  • Lynch G, Kramar EA, Rex CS, et al. Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in mouse model of Huntington’s disease. J Neurosci Off J Soc Neurosci. 2007 Apr 18;27(16):4424–4434.
  • Martínez-Serrano A, Björklund A. Protection of the neostriatum against excitotoxic damage by neurotrophin-producing, genetically modified neural stem cells. J Neurosci Off J Soc Neurosci. 1996 Aug 1;16(15):4604–4616.
  • Pérez-Navarro E, Canudas AM, Akerund P, et al. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 prevent the death of striatal projection neurons in a rodent model of Huntington’s disease. J Neurochem. 2000 Nov;75(5):2190–2199. doi:10.1046/j.1471-4159.2000.0752190.x.
  • Kordower JH. AAV2-neurturin for Parkinson’s disease: what lessons have we learned? Methods Mol Biol Clifton NJ. 2016;1382:485–490.
  • Joyce N, Annett G, Wirthlin L, et al. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med. 2010 Nov;5(6):933–946. doi:10.2217/rme.10.72.
  • Kidd S, Spaeth E, Dembinski JL, et al. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells Dayt Ohio. 2009 Oct;27(10):2614–2623. doi:10.1002/stem.187.
  • Fink KD, Deng P, Torrest A, et al. Developing stem cell therapies for juvenile and adult-onset Huntington’s disease. Regen Med. 2015;10(5):623–646. doi:10.2217/rme.15.25.
  • Meyerrose T, Olson S, Pontow S, et al. Mesenchymal stem cells for the sustained in vivo delivery of bioactive factors. Adv Drug Deliv Rev. 2010 Sep 30;62(12):1167–1174.
  • Meyerrose TE, Roberts M, Ohlemiller KK, et al. Lentiviral-transduced human mesenchymal stem cells persistently express therapeutic levels of enzyme in a xenotransplantation model of human disease. Stem Cells Dayt Ohio. 2008 Jul;26(7):1713–1722. doi:10.1634/stemcells.2008-0008.
  • Bauer G, Dao MA, Case SS, et al. In vivo biosafety model to assess the risk of adverse events from retroviral and lentiviral vectors. Mol Ther J Am Soc Gene Ther. 2008 Jul;16(7):1308–1315. doi:10.1038/mt.2008.93.
  • Petrou P, Gothelf Y, Argov Z, et al. Safety and clinical effects of Mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA Neurol. 2016;73(3):337–344.
  • Zhao C-P, Zhang C, Zhou S-N, et al. Human mesenchymal stromal cells ameliorate the phenotype of SOD1-G93A ALS mice. Cytotherapy. 2007;9(5):414–426. doi:10.1080/14653240701376413.
  • Macias M, Nowicka D, Czupryn A, et al. Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers. BMC Neurosci. 2009;10:144. doi:10.1186/1471-2202-10-144.
  • Rong R, Meng B-L, Jiang N, et al. Roles of BDNF in spinal neuroplasticity in cats subjected to partial dorsal ganglionectomy. Growth Factors Chur Switz. 2011 Dec;29(6):263–270. doi:10.3109/08977194.2011.606786.
  • Vavrek R, Girgis J, Tetzlaff W, et al. BDNF promotes connections of corticospinal neurons onto spared descending interneurons in spinal cord injured rats. Brain J Neurol. 2006 Jun;129(Pt 6):1534–1545. doi:10.1093/brain/awl087.
  • Navarro X, Vivó M, Valero-Cabré A. Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol. 2007 Jul;82(4):163–201. doi:10.1016/j.pneurobio.2007.06.005.
  • Terenghi G. Peripheral nerve regeneration and neurotrophic factors. J Anat. 1999 Jan;194(Pt 1):1–14. doi:10.1046/j.1469-7580.1999.19410001.x.
  • Uchida H, Matsushita Y, Ueda H. Epigenetic regulation of BDNF expression in the primary sensory neurons after peripheral nerve injury: implications in the development of neuropathic pain. Neuroscience. 2013 Jun 14;240:147–154. doi:10.1016/j.neuroscience.2013.02.053.
  • Boyd JG, Gordon T. Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor sustain the axonal regeneration of chronically axotomized motoneurons in vivo. Exp Neurol. 2003 Oct;183(2):610–619. doi:10.1016/S0014-4886(03)00183-3.
  • Takemura Y, Imai S, Kojima H, et al. Brain-derived neurotrophic factor from bone marrow-derived cells promotes post-injury repair of peripheral nerve. PloS One. 2012;7(9):e44592. doi:10.1371/journal.pone.0044592.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.