Stem cell treatments for amyotrophic lateral sclerosis: a critical overview of early phase trials

References

• Goutman SA. Diagnosis and clinical management of amyotrophic lateral sclerosis and other motor neuron disorders. Continuum (Minneap Minn). 2017 Oct;23(5, Peripheral Nerve and Motor Neuron Disorders):1332–1359.
   PubMedGoogle Scholar
• Ringholz GM, Appel SH, Bradshaw M, et al. Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology. 2005 Aug 23;65(4):586–590.
   PubMed Web of Science ®Google Scholar
• Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med. 2017 Jul 13;377(2):162–172.
   PubMed Web of Science ®Google Scholar
• Goutman SA, Nowacek DG, Burke JF, et al. Minorities, men, and unmarried amyotrophic lateral sclerosis patients are more likely to die in an acute care facility. Amyotroph Lateral Scler Frontotemporal Degener. 2014 Sep;15(5–6):440–443.
   PubMed Web of Science ®Google Scholar
• Goutman SA, Chen KS, Paez-Colasante X, et al. Emerging understanding of the genotype-phenotype relationship in amyotrophic lateral sclerosis. Handb Clin Neurol. 2018;148:603–623.
   PubMedGoogle Scholar
• Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994 Mar 3;330(9):585–591.
   PubMed Web of Science ®Google Scholar
• Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017 Jul;16(7):505–512.
   PubMed Web of Science ®Google Scholar
• Mitsumoto H, Brooks BR, Silani V. Clinical trials in amyotrophic lateral sclerosis: why so many negative trials and how can trials be improved? Lancet Neurol. 2014 Nov;13(11):1127–1138.
   PubMed Web of Science ®Google Scholar
• Gage FH. Mammalian neural stem cells. Science (New York, NY). 2000 Feb 25;287(5457):1433–1438.
   Google Scholar
• Temple S. The development of neural stem cells. Nature. 2001 Nov 1;414(6859):112–117.
   PubMed Web of Science ®Google Scholar
• Boulis NM, Federici T, Glass JD, et al. Translational stem cell therapy for amyotrophic lateral sclerosis. Nat Rev Neurol. 2011;8(3):172–176.
   PubMed Web of Science ®Google Scholar
• Lopez-Gonzalez R, Kunckles P, Velasco I. Transient recovery in a rat model of familial amyotrophic lateral sclerosis after transplantation of motor neurons derived from mouse embryonic stem cells. Cell Transplant. 2009;18(10):1171–1181.
   PubMed Web of Science ®Google Scholar
• Maragakis NJ. Stem cells and the ALS neurologist. Amyotrophic Lateral Sclerosis. 2010 Oct;11(5):417–423.
   PubMed Web of Science ®Google Scholar
• Lunn JS, Sakowski SA, Feldman EL. Concise review: stem cell therapies for amyotrophic lateral sclerosis: recent advances and prospects for the future. Stem Cells. 2014 May;32(5):1099–1109.
   PubMed Web of Science ®Google Scholar
• Goutman SA, Chen KS, Feldman EL. Recent advances and the future of stem cell therapies in amyotrophic lateral sclerosis. Neurotherapeutics. 2015 Apr;12(2):428–448.
   PubMed Web of Science ®Google Scholar
• Chen R, Ende N. The potential for the use of mononuclear cells from human umbilical cord blood in the treatment of amyotrophic lateral sclerosis in SOD1 mice. J Med. 2000;31(1–2):21–30.
   PubMedGoogle Scholar
• Ende N, Weinstein F, Chen R, et al. Human umbilical cord blood effect on sod mice (amyotrophic lateral sclerosis). Life Sci. 2000 May 26;67(1):53–59.
   PubMed Web of Science ®Google Scholar
• Garbuzova-Davis S, Willing AE, Zigova T, et al. Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J Hematotherapy Stem Cell Res. 2003 Jun;12(3):255–270.
   PubMedGoogle Scholar
• Garbuzova-Davis S, Sanberg CD, Kuzmin-Nichols N, et al. Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose. PloS One. 2008;3(6):e2494.
   PubMed Web of Science ®Google Scholar
• Ilieva H, Polymenidou M, Cleveland DW. Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol. 2009 Dec 14;187(6):761–772.
   PubMed Web of Science ®Google Scholar
• Cabanes C, Bonilla S, Tabares L, et al. Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration. Neurobiol Dis. 2007 May;26(2):408–418.
   PubMed Web of Science ®Google Scholar
• Lepore AC, Rauck B, Dejea C, et al. Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat Neurosci. 2008 Nov;11(11):1294–1301.
   PubMed Web of Science ®Google Scholar
• Ohnishi S, Ito H, Suzuki Y, et al. Intra-bone marrow-bone marrow transplantation slows disease progression and prolongs survival in G93A mutant SOD1 transgenic mice, an animal model mouse for amyotrophic lateral sclerosis. Brain Res. 2009 Nov 3;1296:216–224.
   PubMed Web of Science ®Google Scholar
• Corti S, Nizzardo M, Nardini M, et al. Systemic transplantation of c-kit+ cells exerts a therapeutic effect in a model of amyotrophic lateral sclerosis. Hum Mol Genet. 2010 Oct 1;19(19):3782–3796.
   PubMed Web of Science ®Google Scholar
• Martin LJ, Liu Z. Adult olfactory bulb neural precursor cell grafts provide temporary protection from motor neuron degeneration, improve motor function, and extend survival in amyotrophic lateral sclerosis mice. J Neuropathol Exp Neurol. 2007 Nov;66(11):1002–1018.
   PubMed Web of Science ®Google Scholar
• Suzuki M, McHugh J, Tork C, et al. Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS. Mol Ther. 2008 Dec;16(12):2002–2010.
   PubMed Web of Science ®Google Scholar
• Krakora D, Mulcrone P, Meyer M, et al. Synergistic effects of GDNF and VEGF on lifespan and disease progression in a familial ALS rat model. Mol Ther. 2013 Aug;21(8):1602–1610.
   PubMed Web of Science ®Google Scholar
• Corti S, Locatelli F, Papadimitriou D, et al. Neural stem cells LewisX+ CXCR4+ modify disease progression in an amyotrophic lateral sclerosis model. Brain. 2007 May;130(Pt 5):1289–1305.
   PubMedGoogle Scholar
• Klein SM, Behrstock S, McHugh J, et al. GDNF delivery using human neural progenitor cells in a rat model of ALS. Hum Gene Ther. 2005 Apr;16(4):509–521.
   PubMed Web of Science ®Google Scholar
• Hwang DH, Lee HJ, Park IH, et al. Intrathecal transplantation of human neural stem cells overexpressing VEGF provide behavioral improvement, disease onset delay and survival extension in transgenic ALS mice. Gene Ther. 2009 Oct;16(10):1234–1244.
   PubMed Web of Science ®Google Scholar
• Park S, Kim HT, Yun S, et al. Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice. Exp Mol Med. 2009 Jul 31;41(7):487–500.
   PubMed Web of Science ®Google Scholar
• Robinton DA, Daley GQ. The promise of induced pluripotent stem cells in research and therapy. Nature. 2012 Jan 18;481(7381):295–305.
   PubMed Web of Science ®Google Scholar
• Sareen D, Gowing G, Sahabian A, et al. Human induced pluripotent stem cells are a novel source of neural progenitor cells (iNPCs) that migrate and integrate in the rodent spinal cord. J Comp Neurol. 2014 Aug 15;522(12):2707–2728.
   PubMed Web of Science ®Google Scholar
• Blanquer M, Perez-Espejo MA, Martinez-Lage JF, et al. A surgical technique of spinal cord cell transplantation in amyotrophic lateral sclerosis. J Neurosci Methods. 2010 Aug 30;191(2):255–257.
   PubMed Web of Science ®Google Scholar
• Chen L, Huang H, Zhang J, et al. Short-term outcome of olfactory ensheathing cells transplantation for treatment of amyotrophic lateral sclerosis. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2007 Sep;21(9):961–966.
   PubMedGoogle Scholar
• Deng J, Zou ZM, Zhou TL, et al. Bone marrow mesenchymal stem cells can be mobilized into peripheral blood by G-CSF in vivo and integrate into traumatically injured cerebral tissue. Neurol Sci. 2011 Aug;32(4):641–651.
   PubMed Web of Science ®Google Scholar
• Tanaka M, Kikuchi H, Ishizu T, et al. Intrathecal upregulation of granulocyte colony stimulating factor and its neuroprotective actions on motor neurons in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 2006 Aug;65(8):816–825.
   PubMed Web of Science ®Google Scholar
• Mazzini L, Mareschi K, Ferrero I, et al. Stem cell treatment in Amyotrophic Lateral Sclerosis. J Neurol Sci. 2008 Feb 15;265(1–2):78–83.
   PubMed Web of Science ®Google Scholar
• Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008 Sep;8(9):726–736.
   PubMed Web of Science ®Google Scholar
• Karussis D, Karageorgiou C, Vaknin-Dembinsky A, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187–1194.
   PubMed Web of Science ®Google Scholar
• Woodbury D, Schwarz EJ, Prockop DJ, et al. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000 Aug 15;61(4):364–370.
   PubMed Web of Science ®Google Scholar
• Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol. 2000 Aug;164(2):247–256.
   PubMed Web of Science ®Google Scholar
• Bossolasco P, Cova L, Calzarossa C, et al. Neuro-glial differentiation of human bone marrow stem cells in vitro. Exp Neurol. 2005 Jun;193(2):312–325.
   PubMed Web of Science ®Google Scholar
• Lu P, Blesch A, Tuszynski MH. Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact? J Neurosci Res. 2004 Jul 15;77(2):174–191.
   PubMed Web of Science ®Google Scholar
• Ciervo Y, Ning K, Jun X, et al. Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis. Mol Neurodegener. 2017 Nov 13;12(1):85.
   PubMedGoogle Scholar
• Marconi S, Bonaconsa M, Scambi I, et al. Systemic treatment with adipose-derived mesenchymal stem cells ameliorates clinical and pathological features in the amyotrophic lateral sclerosis murine model. Neuroscience. 2013 Sep 17;248:333–343.
   PubMed Web of Science ®Google Scholar
• Ramon-Cueto A, Valverde F. Olfactory bulb ensheathing glia: a unique cell type with axonal growth-promoting properties. Glia. 1995 Jul;14(3):163–173.
   PubMed Web of Science ®Google Scholar
• Lipson AC, Widenfalk J, Lindqvist E, et al. Neurotrophic properties of olfactory ensheathing glia. Exp Neurol. 2003 Apr;180(2):167–171.
   PubMed Web of Science ®Google Scholar
• Huang H, Chen L, Xi H, et al. Fetal olfactory ensheathing cells transplantation in amyotrophic lateral sclerosis patients: a controlled pilot study. Clin Transplant. 2008 Nov-Dec;22(6):710–718.
   PubMed Web of Science ®Google Scholar
• Chen L, Chen D, Xi H, et al. Olfactory ensheathing cell neurorestorotherapy for amyotrophic lateral sclerosis patients: benefits from multiple transplantations. Cell Transplant. 2012;21(Suppl 1):S65–77.
   PubMed Web of Science ®Google Scholar
• Guo X, Johe K, Molnar P, et al. Characterization of a human fetal spinal cord stem cell line, NSI-566RSC, and its induction to functional motoneurons. J Tissue Eng Regen Med. 2010;4(3):181–193.
   PubMed Web of Science ®Google Scholar
• Xu L, Yan J, Chen D, et al. Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats. Transplantation. 2006 Oct 15;82(7):865–875.
   PubMed Web of Science ®Google Scholar
• Hefferan MP, Galik J, Kakinohana O, et al. Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation. PloS One. 2012;7(8):e42614.
   PubMed Web of Science ®Google Scholar
• Chen KS, McGinley LM, Kashlan ON, et al. Targeted intraspinal injections to assess therapies in rodent models of neurological disorders. Nat Protoc. 2019 Feb;14(2):331–349.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Wang L, Fu Y, et al. Preliminary investigation of effect of granulocyte colony stimulating factor on amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis. 2009 Oct-Dec;10(5–6):430–431.
   PubMed Web of Science ®Google Scholar
• Atassi N, Berry J, Shui A, et al. The PRO-ACT database: design, initial analyses, and predictive features. Neurology. 2014 Nov 4;83(19):1719–1725.
   PubMed Web of Science ®Google Scholar
• Nefussy B, Artamonov I, Deutsch V, et al. Recombinant human granulocyte-colony stimulating factor administration for treating amyotrophic lateral sclerosis: A pilot study. Amyotrophic Lateral Sclerosis. 2010;11(1–2):187–193.
   PubMed Web of Science ®Google Scholar
• Tarella C, Rutella S, Gualandi F, et al. Consistent bone marrow-derived cell mobilization following repeated short courses of granulocyte-colony-stimulating factor in patients with amyotrophic lateral sclerosis: results from a multicenter prospective trial. Cytotherapy. 2010;12(1):50–59.
   PubMed Web of Science ®Google Scholar
• Chio A, Mora G, La Bella V, et al. Repeated courses of granulocyte colony-stimulating factor in amyotrophic lateral sclerosis: clinical and biological results from a prospective multicenter study. Muscle Nerve. 2011 Feb;43(2):189–195.
   PubMed Web of Science ®Google Scholar
• Cashman N, Tan LY, Krieger C, et al. Pilot study of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells in amyotrophic lateral sclerosis (ALS). Muscle Nerve. 2008 May;37(5):620–625.
   PubMed Web of Science ®Google Scholar
• Appel SH, Engelhardt JI, Henkel JS, et al. Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology. 2008 Oct 21;71(17):1326–1334.
   PubMed Web of Science ®Google Scholar
• Janson CG, Ramesh TM, During MJ, et al. Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis. J Hematotherapy Stem Cell Res. 2001 Dec;10(6):913–915.
   PubMedGoogle Scholar
• Martinez HR, Gonzalez-Garza MT, Moreno-Cuevas JE, et al. Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients. Cytotherapy. 2009;11(1):26–34.
   PubMed Web of Science ®Google Scholar
• Martinez HR, Molina-Lopez JF, Gonzalez-Garza MT, et al. Stem cell transplantation in amyotrophic lateral sclerosis patients: methodological approach, safety, and feasibility. Cell Transplant. 2012;21(9):1899–1907.
   PubMed Web of Science ®Google Scholar
• Prabhakar S, Marwaha N, Lal V, et al. Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study. Neurol India. 2012 Sep-Oct;60(5):465–469.
   PubMed Web of Science ®Google Scholar
• Nabavi SM, Arab L, Jarooghi N, et al. Safety, feasibility of intravenous and intrathecal injection of autologous bone marrow derived mesenchymal stromal cells in patients with amyotrophic lateral sclerosis: an open label phase i clinical trial. Cell J. 2019 Jan;20(4):592–598.
   PubMed Web of Science ®Google Scholar
• Sykova E, Rychmach P, Drahoradova I, et al. Transplantation of mesenchymal stromal cells in patients with amyotrophic lateral sclerosis: results of phase I/IIa clinical trial. Cell Transplant. 2017 Apr 13;26(4):647–658.
   PubMed Web of Science ®Google Scholar
• Sobus A, Baumert B, Litwinska Z, et al. Safety and feasibility of lin- cells administration to ALS patients: a novel view on humoral factors and miRNA profiles. Int J Mol Sci. 2018 Apr 27;19(5):1312.
   PubMed Web of Science ®Google Scholar
• Oh KW, Moon C, Kim HY, et al. Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Transl Med. 2015 May 1;4:590–597.
   Web of Science ®Google Scholar
• Oh KW, Noh MY, Kwon MS, et al. Repeated intrathecal mesenchymal stem cells for amyotrophic lateral sclerosis. Ann Neurol. 2018 Sep;84(3):361–373.
   PubMed Web of Science ®Google Scholar
• Mazzini L, Ferrero I, Luparello V, et al. Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: a Phase I clinical trial. Exp Neurol. 2010 May;223(1):229–237.
   PubMed Web of Science ®Google Scholar
• Mazzini L, Mareschi K, Ferrero I, et al. Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol Res. 2006 Jul;28(5):523–526.
   PubMed Web of Science ®Google Scholar
• Mazzini L, Mareschi K, Ferrero I, et al. Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study. Cytotherapy. 2012 Jan;14(1):56–60.
   PubMed Web of Science ®Google Scholar
• Blanquer M, Moraleda JM, Iniesta F, et al. Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study. Stem Cells. 2012;30(6):1277–1285.
   PubMed Web of Science ®Google Scholar
• Ruiz-Lopez FJ, Guardiola J, Izura V, et al. Breathing pattern in a phase I clinical trial of intraspinal injection of autologous bone marrow mononuclear cells in patients with amyotrophic lateral sclerosis. Respir Physiol Neurobiol. 2016 Jan 15;221:54–58.
   PubMed Web of Science ®Google Scholar
• Deda H, Inci MC, Kurekci AE, et al. Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up. Cytotherapy. 2009;11(1):18–25.
   PubMed Web of Science ®Google Scholar
• Baek W, Kim YS, Koh SH, et al. Stem cell transplantation into the intraventricular space via an Ommaya reservoir in a patient with amyotrophic lateral sclerosis. J Neurosurg Sci. 2012 Sep;56(3):261–263.
   PubMed Web of Science ®Google Scholar
• Murdock BJ, Zhou T, Kashlan SR, et al. Correlation of peripheral immunity with rapid amyotrophic lateral sclerosis progression. JAMA Neurol. 2017;74(12):1446–1454.
   PubMed Web of Science ®Google Scholar
• Murdock BJ, Bender DE, Kashlan SR, et al. Increased ratio of circulating neutrophils to monocytes in amyotrophic lateral sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016 Aug;3(4):e242.
   PubMed Web of Science ®Google Scholar
• Murdock BJ, Bender DE, Segal BM, et al. The dual roles of immunity in ALS: injury overrides protection. Neurobiol Dis. 2015;77:1–12.
   PubMed Web of Science ®Google Scholar
• Moviglia GA, Moviglia-Brandolino MT, Varela GS, et al. Feasibility, safety, and preliminary proof of principles of autologous neural stem cell treatment combined with T-cell vaccination for ALS patients. Cell Transplant. 2012;21(Suppl 1):S57–63.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Staff NP, Madigan NN, Morris J, et al. Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS. Neurology. 2016 Nov 22;87(21):2230–2234.
   PubMed Web of Science ®Google Scholar
• Chew S, Khandji AG, Montes J, et al. Olfactory ensheathing glia injections in Beijing: misleading patients with ALS. Amyotrophic Lateral Sclerosis. 2007 Oct;8(5):314–316.
   PubMed Web of Science ®Google Scholar
• Piepers S. van den Berg LH. No benefits from experimental treatment with olfactory ensheathing cells in patients with ALS. Amyotrophic Lateral Sclerosis. 2010 May 3;11(3):328–330.
   PubMed Web of Science ®Google Scholar
• Giordana MT, Grifoni S, Votta B, et al. Neuropathology of olfactory ensheathing cell transplantation into the brain of two amyotrophic lateral sclerosis (ALS) patients. Brain Pathol. 2010 Jul;20(4):730–737.
   PubMed Web of Science ®Google Scholar
• Riley J, Federici T, Polak M, et al. Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I safety trial, technical note, and lumbar safety outcomes. Neurosurgery. 2012 Aug;71(2):405–16; discussion 416.
   PubMed Web of Science ®Google Scholar
• Glass JD, Boulis NM, Johe K, et al. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients. Stem Cells. 2012 Jun;30(6):1144–1151.
   PubMed Web of Science ®Google Scholar
• Riley J, Glass J, Feldman EL, et al. Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I trial, cervical microinjection, and final surgical safety outcomes. Neurosurgery. 2014 Jan;74(1):77–87.
   PubMed Web of Science ®Google Scholar
• Feldman EL, Boulis NM, Hur J, et al. Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes. Ann Neurol. 2014 Mar;75(3):363–373.
   PubMed Web of Science ®Google Scholar
• Tadesse T, Gearing M, Senitzer D, et al. Analysis of graft survival in a trial of stem cell transplant in ALS. Ann Clin Transl Neurol. 2014;1(11):900–908.
   PubMed Web of Science ®Google Scholar
• Glass JD, Hertzberg VS, Boulis NM, et al. Transplantation of spinal cord-derived neural stem cells for ALS: analysis of phase 1 and 2 trials. Neurology. 2016 Jul 26;87(4):392–400.
   PubMed Web of Science ®Google Scholar
• Goutman SA, Brown MB, Glass JD, et al. Long-term Phase 1/2 intraspinal stem cell transplantation outcomes in ALS. Ann Clin Transl Neurol. 2018 Jun;5(6):730–740.
   PubMed Web of Science ®Google Scholar
• Mazzini L, Gelati M, Profico DC, et al. Human neural stem cell transplantation in ALS: initial results from a phase I trial. J Transl Med. 2015;13:17.
   PubMed Web of Science ®Google Scholar
• Gowing G, Shelley B, Staggenborg K, et al. Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats. Neuroreport. 2014 Apr 16;25(6):367–372.
   PubMed Web of Science ®Google Scholar
• Julian K, Yuhasz N, Hollingsworth E, et al. The “growing” reality of the neurological complications of global “stem cell tourism”. Semin Neurol. 2018 Apr;38(2):176–181.
   PubMed Web of Science ®Google Scholar
• Bowman M, Racke M, Kissel J, et al. Responsibilities of health care professionals in counseling and educating patients with incurable neurological diseases regarding “stem cell tourism”: caveat emptor. JAMA Neurol. 2015;72:1342.
   PubMed Web of Science ®Google Scholar
• Cote DJ, Bredenoord AL, Smith TR, et al. Ethical clinical translation of stem cell interventions for neurologic disease. Neurology. 2017 Jan 17;88(3):322–328.
   PubMed Web of Science ®Google Scholar
• Almeida S, Gascon E, Tran H, et al. Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathol. 2013 Sep;126(3):385–399.
   PubMed Web of Science ®Google Scholar
• Richard JP, Maragakis NJ. Induced pluripotent stem cells from ALS patients for disease modeling. Brain Res. 2015 May 14;1607:15–25.
   PubMed Web of Science ®Google Scholar
• Simon NG, Turner MR, Vucic S, et al. Quantifying disease progression in amyotrophic lateral sclerosis. Ann Neurol. 2014 Nov;76(5):643–657.
   PubMed Web of Science ®Google Scholar
• Turner MR, Bowser R, Bruijn L, et al. Mechanisms, models and biomarkers in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013 May;14(Suppl 1):19–32.
   PubMed Web of Science ®Google Scholar
• Paganoni S, Macklin EA, Lee A, et al. Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotroph Lateral Scler Frontotemporal Degener. 2014 Sep;15(5–6):453–456.
   PubMed Web of Science ®Google Scholar
• Vu LT, Bowser R. Fluid-based biomarkers for amyotrophic lateral sclerosis. Neurotherapeutics. 2017 Jan;14(1):119–134.
   PubMed Web of Science ®Google Scholar
• Foerster BR, Welsh RC, Feldman EL. 25 years of neuroimaging in amyotrophic lateral sclerosis. Nat Rev Neurol. 2013 Sep;9(9):513–524.
   PubMed Web of Science ®Google Scholar