Exploring the Role of Stem Cell Therapy in Treating Neurodegenerative
Diseases: Challenges and Current Perspectives

Nidhi       Puranik; Ananta    Prasad    Arukha; Shiv    Kumar    Yadav; Dhananjay       Yadav; Jun    O.   Jin
doi:10.2174/1574888X16666210810103838
Abstract

Several human neurological disorders, such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, spinal cord injury, multiple sclerosis, and brain stroke, are caused by the injury to neurons or glial cells. The recent years have witnessed the successful generation of neurons and glia cells driving efforts to develop stem-cell-based therapies for patients to combat a broad spectrum of human neurological diseases. The inadequacy of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. Attempts are thus being made to reconstruct viable neurons and glial cells from different stem cells, such as embryonic stem cells, mesenchymal stem cells, and neural stem cells. Dedicated research to cultivate stem cell-based brain transplantation therapies has been carried out. We aim at compiling the breakthroughs in the field of stem cell-based therapy for the treatment of neurodegenerative maladies, emphasizing the shortcomings faced, victories achieved, and the future prospects of the therapy in clinical settings.
Keywords: Neurodegenerative disorders, stem cell therapy, neurons, neural stem cell, induced pluripotent stem cells, growth factors.
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[1] 
Galli R, Gritti A, Bonfanti L, Vescovi AL. Neural stem cells: An overview. Circ Res  2003; 92(6): 598-608.
[http://dx.doi.org/10.1161/01.RES.0000065580.02404.F4] [PMID: 12676811] 
[2] 
Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: Models, mechanisms, and a new hope. Dis Model Mech  2017; 10(5): 499-502.
[3] 
Kalia LV, Lang AE. Parkinson disease in 2015: Evolving basic, pathological and clinical concepts in PD. Nat Rev Neurol  2016; 12(2): 65-6.
[http://dx.doi.org/10.1038/nrneurol.2015.249] [PMID: 26782330] 
[4] 
Šimić G, Babić Leko M, Wray S, et al. Monoaminergic neuropathology in Alzheimer’s disease. Prog Neurobiol  2017; 151: 101-38.
[http://dx.doi.org/10.1016/j.pneurobio.2016.04.001] [PMID: 27084356] 
[5] 
Weller J, Budson A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000 Res  2018; 7: F1000 Faculty Rev-1161.
[http://dx.doi.org/10.12688/f1000research.14506.1] [PMID: 30135715] 
[6] 
Rahim F, Shirbandi K, Akbari R. Stem cell therapy for multiple sclerosis: An exciting challenge or a treatment hope.Stem Cell transplantation for autoimmune diseases and inflammation. Berlin, Germany: Springer 2019; pp. 45-61.
[http://dx.doi.org/10.1007/978-3-030-23421-8_3] 
[7] 
Paap B, Hecker M, Koczan D, Zettl U. Molecular biomarkers in multiple sclerosis. J Clin Cell Immunol S  2013; 10(4): 34-65.
[8] 
Glorioso JC, Cohen JB, Carlisle DL, Munoz-Sanjuan I, Friedlander RM. Moving toward a gene therapy for Huntington’s disease. Gene Ther  2015; 22(12): 931-3.
[http://dx.doi.org/10.1038/gt.2015.102] [PMID: 26633828] 
[9] 
Petcu EB, Sherwood K, Popa-Wagner A, Buga AM, Aceti L, Miroiu RI. Artistic skills recovery and compensation in visual artists after stroke. Front Neurol  2016; 7: 76-6.
[http://dx.doi.org/10.3389/fneur.2016.00076] [PMID: 27242659] 
[10] 
Fan Y, Winanto , Ng SY. Replacing what's lost: A new era of stem cell therapy for Parkinson's disease. Transl Neurodegener  2020; 9(1): 2.
[http://dx.doi.org/10.1186/s40035-019-0180-x] [PMID: 31911835] 
[11] 
Barker RA, Parmar M, Studer L, Takahashi J. Human trials of stem cell-derived dopamine neurons for Parkinson’s disease: Dawn of a new era. Cell Stem Cell  2017; 21(5): 569-73.
[http://dx.doi.org/10.1016/j.stem.2017.09.014] [PMID: 29100010] 
[12] 
Ahmed J, Rahman H. Progression of treating Alzheimer’s disease with stem cell-based therapies. Int Ann Sci  2020; 8(1): 38-46.
[http://dx.doi.org/10.21467/ias.8.1.38-46] 
[13] 
Kerkis I, da Silva JM, Wenceslau CV, Mambelli-Lisboa NC, Frare EO. Brain-derived neurotrophic factor and stem cell-based technologies in huntington’s disease therapy. In: Tunalı NE, Ed. Neurodegenerative diseases-molecular mechanisms and current therapeutic approaches. London, UK: IntechOpen 2020; 1: p. 1.
[http://dx.doi.org/10.5772/intechopen.91226] 
[14] 
Sarkar P, Rice CM, Scolding NJ. Cell therapy for multiple sclerosis. CNS Drugs  2017; 31(6): 453-69.
[http://dx.doi.org/10.1007/s40263-017-0429-9] [PMID: 28397112] 
[15] 
Liu X, Ye R, Yan T, et al. Cell based therapies for ischemic stroke: From basic science to bedside. Prog Neurobiol  2014; 115: 92-115.
[http://dx.doi.org/10.1016/j.pneurobio.2013.11.007] [PMID: 24333397] 
[16] 
Amariglio N, Hirshberg A, Scheithauer BW, et al. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med  2009; 6(2): e1000029.
[http://dx.doi.org/10.1371/journal.pmed.1000029] [PMID: 19226183] 
[17] 
Meamar R, Nasr-Esfahani MH, Mousavi SA, Basiri K. Stem cell therapy in amyotrophic lateral sclerosis. J Clin Neurosci  2013; 20(12): 1659-63.
[http://dx.doi.org/10.1016/j.jocn.2013.04.024] [PMID: 24148693] 
[18] 
Enzmann GU, Benton RL, Talbott JF, Cao Q, Whittemore SR. Functional considerations of stem cell transplantation therapy for spinal cord repair. J Neurotrauma  2006; 23(3-4): 479-95.
[http://dx.doi.org/10.1089/neu.2006.23.479] [PMID: 16629631] 
[19] 
Assinck P, Duncan GJ, Hilton BJ, Plemel JR, Tetzlaff W. Cell transplantation therapy for spinal cord injury. Nat Neurosci  2017; 20(5): 637-47.
[http://dx.doi.org/10.1038/nn.4541] [PMID: 28440805] 
[20] 
Tate CC, Shear DA, Tate MC, Archer DR, Stein DG, LaPlaca MC. Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain. J Tissue Eng Regen Med  2009; 3(3): 208-17.
[http://dx.doi.org/10.1002/term.154] [PMID: 19229887] 
[21] 
Rosser AE, Zietlow R, Dunnett SB. Stem cell transplantation for neurodegenerative diseases. Curr Opin Neurol  2007; 20(6): 688-92.
[http://dx.doi.org/10.1097/WCO.0b013e3282f132fc] [PMID: 17992090] 
[22] 
Dantuma E, Merchant S, Sugaya K. Stem cells for the treatment of neurodegenerative diseases. Stem Cell Res Ther  2010; 1(5): 37.
[http://dx.doi.org/10.1186/scrt37] [PMID: 21144012] 
[23] 
Nadig RR. Stem cell therapy-Hype or hope? A review. J Conserv Dent  2009; 12(4): 131-8.
[http://dx.doi.org/10.4103/0972-0707.58329] [PMID: 20543921] 
[24] 
Chagastelles PC, Nardi NB. Biology of stem cells: An overview. Kidney Int Suppl  2011; 1(3): 63-7.
[http://dx.doi.org/10.1038/kisup.2011.15] 
[25] 
De Luca M, Aiuti A, Cossu G, Parmar M, Pellegrini G, Robey PG. Advances in stem cell research and therapeutic development. Nat Cell Biol  2019; 21(7): 801-11.
[http://dx.doi.org/10.1038/s41556-019-0344-z] [PMID: 31209293] 
[26] 
Lunn JS, Sakowski SA, Hur J, Feldman EL. Stem cell technology for neurodegenerative diseases. Ann Neurol  2011; 70(3): 353-61.
[http://dx.doi.org/10.1002/ana.22487] [PMID: 21905078] 
[27] 
Kim SU, Lee HJ, Kim YB. Neural stem cell-based treatment for neurodegenerative diseases. Neuropathology  2013; 33(5): 491-504.
[http://dx.doi.org/10.1111/neup.12020] [PMID: 23384285] 
[28] 
Lindvall O, Kokaia Z, Martinez-Serrano A. Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat Med  2004; (10 Suppl): S42-50.
[http://dx.doi.org/10.1038/nm1064] [PMID: 15272269] 
[29] 
Lee JH, Oh I-H, Lim HK. Stem cell therapy: A prospective treatment for Alzheimer’s disease. Psychiatry Investig  2016; 13(6): 583-9.
[http://dx.doi.org/10.4306/pi.2016.13.6.583] [PMID: 27909447] 
[30] 
Sanberg PR, Willing AE, Garbuzova-Davis S, et al. Umbilical cord blood-derived stem cells and brain repair. Ann N Y Acad Sci  2005; 1049: 67-83.
[http://dx.doi.org/10.1196/annals.1334.008] [PMID: 15965108] 
[31] 
Harris DT. Cord blood stem cells: A review of potential neurological applications. Stem Cell Rev  2008; 4(4): 269-74.
[http://dx.doi.org/10.1007/s12015-008-9039-8] [PMID: 18679834] 
[32] 
Guo Z, Zhang L, Wu Z, Chen Y, Wang F, Chen G. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimer’s disease model. Cell Stem Cell  2014; 14(2): 188-202.
[http://dx.doi.org/10.1016/j.stem.2013.12.001] [PMID: 24360883] 
[33] 
Marsh SE, Blurton-Jones M. Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support. Neurochem Int  2017; 106: 94-100.
[http://dx.doi.org/10.1016/j.neuint.2017.02.006] [PMID: 28219641] 
[34] 
Daley GQ. The promise and perils of stem cell therapeutics. Cell Stem Cell  2012; 10(6): 740-9.
[http://dx.doi.org/10.1016/j.stem.2012.05.010] [PMID: 22704514] 
[35] 
De Feo D, Merlini A, Laterza C, Martino G. Neural stem cell transplantation in central nervous system disorders: From cell replacement to neuroprotection. Curr Opin Neurol  2012; 25(3): 322-33.
[http://dx.doi.org/10.1097/WCO.0b013e328352ec45] [PMID: 22547103] 
[36] 
Choi K-A, Hong S. Induced neural stem cells as a means of treatment in Huntington’s disease. Expert Opin Biol Ther  2017; 17(11): 1333-43.
[http://dx.doi.org/10.1080/14712598.2017.1365133] [PMID: 28792249] 
[37] 
Feldman EL, Boulis NM, Hur J, et al. Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: Phase 1 trial outcomes. Ann Neurol  2014; 75(3): 363-73.
[http://dx.doi.org/10.1002/ana.24113] [PMID: 24510776] 
[38] 
Yandava BD, Billinghurst LL, Snyder EY. “Global” cell replacement is feasible via neural stem cell transplantation: Evidence from the dysmyelinated shiverer mouse brain. Proc Natl Acad Sci USA  1999; 96(12): 7029-34.
[http://dx.doi.org/10.1073/pnas.96.12.7029] [PMID: 10359833] 
[39] 
Jeong S-W, Chu K, Jung K-H, Kim SU, Kim M, Roh J-K. Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke  2003; 34(9): 2258-63.
[http://dx.doi.org/10.1161/01.STR.0000083698.20199.1F] [PMID: 12881607] 
[40] 
Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells-current trends and future prospective. Biosci Rep  2015; 35(2): e00191.
[http://dx.doi.org/10.1042/BSR20150025] [PMID: 25797907] 
[41] 
Nombela-Arrieta C, Ritz J, Silberstein LE. The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol  2011; 12(2): 126-31.
[http://dx.doi.org/10.1038/nrm3049] [PMID: 21253000] 
[42] 
Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA. Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med  2010; 5(6): 933-46.
[http://dx.doi.org/10.2217/rme.10.72] [PMID: 21082892] 
[43] 
Sadan O, Shemesh N, Cohen Y, Melamed E, Offen D. Adult neurotrophic factor-secreting stem cells: A potential novel therapy for neurodegenerative diseases. Isr Med Assoc J  2009; 11(4): 201-4.
[PMID: 19603590] 
[44] 
Scopetti M, Santurro A, Gatto V, et al. Mesenchymal stem cells in neurodegenerative diseases: Opinion review on ethical dilemmas. World J Stem Cells  2020; 12(3): 168-77.
[http://dx.doi.org/10.4252/wjsc.v12.i3.168] [PMID: 32266049] 
[45] 
Shroff G. A review on stem cell therapy for multiple sclerosis: Special focus on human embryonic stem cells. Stem Cells Cloning  2018; 11: 1-11.
[http://dx.doi.org/10.2147/SCCAA.S135415] [PMID: 29483778] 
[46] 
Liu L, Huang J-S, Han C, et al. Induced pluripotent stem cells in Huntington’s disease: Disease modeling and the potential for cell-based therapy. Mol Neurobiol  2016; 53(10): 6698-708.
[http://dx.doi.org/10.1007/s12035-015-9601-8] [PMID: 26659595] 
[47] 
Kolagar TA, Farzaneh M, Nikkar N, Khoshnam SE. Human pluripotent stem cells in neurodegenerative diseases: Potentials, advances and limitations. Curr Stem Cell Res Ther  2020; 15(2): 102-10.
[http://dx.doi.org/10.2174/1574888X14666190823142911] [PMID: 31441732] 
[48] 
Kim H-J. Stem cell potential in Parkinson’s disease and molecular factors for the generation of dopamine neurons. Biochim Biophys Acta  2011; 1812(1): 1-11.
[http://dx.doi.org/10.1016/j.bbadis.2010.08.006] [PMID: 20713152] 
[49] 
Zhang X, Hu D, Shang Y, Qi X. Using induced pluripotent stem cell neuronal models to study neurodegenerative diseases. Biochim Biophys Acta Mol Basis Dis  2020; 1866(4): 165431.
[http://dx.doi.org/10.1016/j.bbadis.2019.03.004] [PMID: 30898538] 
[50] 
Sandoe J, Eggan K. Opportunities and challenges of pluripotent stem cell neurodegenerative disease models. Nat Neurosci  2013; 16(7): 780-9.
[http://dx.doi.org/10.1038/nn.3425] [PMID: 23799470] 
[51] 
Nagoshi N, Okano H. Applications of induced pluripotent stem cell technologies in spinal cord injury. J Neurochem  2017; 141(6): 848-60.
[http://dx.doi.org/10.1111/jnc.13986] [PMID: 28199003] 
[52] 
Chau M, Deveau TC, Song M, et al. Transplantation of iPS cell-derived neural progenitors overexpressing SDF-1α increases regeneration and functional recovery after ischemic stroke. Oncotarget  2017; 8(57): 97537-53.
[http://dx.doi.org/10.18632/oncotarget.22180] [PMID: 29228630] 
[53] 
Glass JD. The promise and the reality of stem-cell therapies for neurodegenerative diseases. Cerebrum  2010; 2010: 24.
[54] 
Walczak P, Bulte JW. The role of noninvasive cellular imaging in developing cell-based therapies for neurodegenerative disorders. Neurodegener Dis  2007; 4(4): 306-13.
[http://dx.doi.org/10.1159/000101887] [PMID: 17627134] 
[55] 
Osborn TM, Hallett PJ, Schumacher JM, Isacson O. Advantages and recent developments of autologous cell therapy for Parkinson’s disease patients. Front Cell Neurosci  2020; 14: 58-8.
[http://dx.doi.org/10.3389/fncel.2020.00058] [PMID: 32317934] 
[56] 
Kamelska-Sadowska AM, Wojtkiewicz J, Kowalski IM. Review of the current knowledge on the role of stem cell transplantation in neurorehabilitation. Biomed Res Int  2019; 2019: 3290894.
[http://dx.doi.org/10.1155/2019/3290894] [PMID: 30931325] 
[57] 
Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature  2006; 441(7097): 1094-6.
[http://dx.doi.org/10.1038/nature04960] [PMID: 16810245] 
[58] 
Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med  2001; 344(10): 710-9.
[http://dx.doi.org/10.1056/NEJM200103083441002] [PMID: 11236774] 
[59] 
Lindvall O. Developing dopaminergic cell therapy for Parkinson’s disease-give up or move forward? Mov Disord  2013; 28(3): 268-73.
[http://dx.doi.org/10.1002/mds.25378] [PMID: 23401015] 
[60] 
Lindvall O, Björklund A. Cell therapy in Parkinson’s disease. NeuroRx  2004; 1(4): 382-93.
[http://dx.doi.org/10.1602/neurorx.1.4.382] [PMID: 15717042] 
[61] 
Lindvall O. Stem cells for cell therapy in Parkinson’s disease. Pharmacol Res  2003; 47(4): 279-87.
[http://dx.doi.org/10.1016/S1043-6618(03)00037-9] [PMID: 12644384] 
[62] 
Takahashi J. Stem cell therapy for Parkinson’s disease. Expert Rev Neurother  2007; 7(6): 667-75.
[http://dx.doi.org/10.1586/14737175.7.6.667] [PMID: 17563250] 
[63] 
Fu M-H, Li C-L, Lin H-L, et al. Stem cell transplantation therapy in Parkinson’s disease. Springerplus  2015; 4: 597-7.
[http://dx.doi.org/10.1186/s40064-015-1400-1] [PMID: 26543732] 
[64] 
Perrier AL, Tabar V, Barberi T, et al. Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci USA  2004; 101(34): 12543-8.
[http://dx.doi.org/10.1073/pnas.0404700101] [PMID: 15310843] 
[65] 
Ko J-Y, Park C-H, Koh H-C, et al. Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons. J Neurochem  2007; 103(4): 1417-29.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04898.x] [PMID: 17854346] 
[66] 
Ambasudhan R, Dolatabadi N, Nutter A, Masliah E, Mckercher SR, Lipton SA. Potential for cell therapy in Parkinson’s disease using genetically programmed human embryonic stem cell-derived neural progenitor cells. J Comp Neurol  2014; 522(12): 2845-56.
[http://dx.doi.org/10.1002/cne.23617] [PMID: 24756727] 
[67] 
Kim JH, Auerbach JM, Rodríguez-Gómez JA, et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature  2002; 418(6893): 50-6.
[http://dx.doi.org/10.1038/nature00900] [PMID: 12077607] 
[68] 
Roybon L, Christophersen NS, Brundin P, Li JY. Stem cell therapy for Parkinson’s disease: Where do we stand? Cell Tissue Res  2004; 318(1): 261-73.
[http://dx.doi.org/10.1007/s00441-004-0946-y] [PMID: 15309619] 
[69] 
Chen Y, Shen J, Ke K, Gu X. Clinical potential and current progress of mesenchymal stem cells for Parkinson’s disease: A systematic review. Neurol Sci  2020; 41(5): 1051-61.
[http://dx.doi.org/10.1007/s10072-020-04240-9] [PMID: 31919699] 
[70] 
Politis M, Lindvall O. Clinical application of stem cell therapy in Parkinson’s disease. BMC Med  2012; 10(1): 1-7.
[http://dx.doi.org/10.1186/1741-7015-10-1] [PMID: 22216957] 
[71] 
Lindvall O, Kokaia Z. Prospects of stem cell therapy for replacing dopamine neurons in Parkinson’s disease. Trends Pharmacol Sci  2009; 30(5): 260-7.
[http://dx.doi.org/10.1016/j.tips.2009.03.001] [PMID: 19362379] 
[72] 
Stoddard-Bennett T, Pera RR. Stem cell therapy for Parkinson’s disease: Safety and modeling. Neural Regen Res  2020; 15(1): 36-40.
[http://dx.doi.org/10.4103/1673-5374.264446] [PMID: 31535640] 
[73] 
Takahashi J. Preclinical evaluation of patient-derived cells shows promise for Parkinson’s disease. J Clin Invest  2020; 130(2): 601-3.
[http://dx.doi.org/10.1172/JCI134031] [PMID: 31929191] 
[74] 
Kumar A, Singh A, Ekavali . A review on Alzheimer’s disease pathophysiology and its management: An update. Pharmacol Rep  2015; 67(2): 195-203.
[http://dx.doi.org/10.1016/j.pharep.2014.09.004] [PMID: 25712639] 
[75] 
Reddy AP, Ravichandran J, Carkaci-Salli N. Neural regeneration therapies for Alzheimer’s and Parkinson’s disease-related disorders. Biochim Biophys Acta Mol Basis Dis  2020; 1866(4): 165506.
[http://dx.doi.org/10.1016/j.bbadis.2019.06.020] [PMID: 31276770] 
[76] 
Waldau B, Shetty AK. Behavior of neural stem cells in the Alzheimer brain. Cell Mol Life Sci  2008; 65(15): 2372-84.
[http://dx.doi.org/10.1007/s00018-008-8053-y] [PMID: 18500448] 
[77] 
Cosacak MI, Bhattarai P, Kizil C. Alzheimer’s disease, neural stem cells and neurogenesis: Cellular phase at single-cell level. Neural Regen Res  2020; 15(5): 824-7.
[http://dx.doi.org/10.4103/1673-5374.268896] [PMID: 31719242] 
[78] 
Zhang F-Q, Jiang J-L, Zhang J-T, Niu H, Fu X-Q, Zeng L-L. Current status and future prospects of stem cell therapy in Alzheimer’s disease. Neural Regen Res  2020; 15(2): 242-50.
[http://dx.doi.org/10.4103/1673-5374.265544] [PMID: 31552889] 
[79] 
Duncan T, Valenzuela M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res Ther  2017; 8(1): 111.
[http://dx.doi.org/10.1186/s13287-017-0567-5] [PMID: 28494803] 
[80] 
Fan X, Sun D, Tang X, Cai Y, Yin ZQ, Xu H. Stem-cell challenges in the treatment of Alzheimer’s disease: A long way from bench to bedside. Med Res Rev  2014; 34(5): 957-78.
[http://dx.doi.org/10.1002/med.21309] [PMID: 24500883] 
[81] 
Hunsberger JG, Rao M, Kurtzberg J, et al. Accelerating stem cell trials for Alzheimer’s disease. Lancet Neurol  2016; 15(2): 219-30.
[http://dx.doi.org/10.1016/S1474-4422(15)00332-4] [PMID: 26704439] 
[82] 
Tong LM, Djukic B, Arnold C, et al. Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation. J Neurosci  2014; 34(29): 9506-15.
[http://dx.doi.org/10.1523/JNEUROSCI.0693-14.2014] [PMID: 25031394] 
[83] 
Blurton-Jones M, Kitazawa M, Martinez-Coria H, et al. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci USA  2009; 106(32): 13594-9.
[http://dx.doi.org/10.1073/pnas.0901402106] [PMID: 19633196] 
[84] 
Wu C-C, Lien C-C, Hou W-H, Chiang P-M, Tsai K-J. Gain of BDNF function in engrafted neural stem cells promotes the therapeutic potential for Alzheimer’s disease. Sci Rep  2016; 6(1): 27358.
[http://dx.doi.org/10.1038/srep27358] [PMID: 27264956] 
[85] 
Kim S, Chang K-A, Kim Ja, et al. The preventive and therapeutic effects of intravenous human adipose-derived stem cells in Alzheimer’s disease mice. PLoS One  2012; 7(9): e45757-7.
[http://dx.doi.org/10.1371/journal.pone.0045757] [PMID: 23049854] 
[86] 
Ager RR, Davis JL, Agazaryan A, et al. Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer’s disease and neuronal loss. Hippocampus  2015; 25(7): 813-26.
[http://dx.doi.org/10.1002/hipo.22405] [PMID: 25530343] 
[87] 
Hinkle JL, Guanci MM. Acute ischemic stroke review. J Neurosci Nurs  2007; 39(5): 285-293, 310.
[http://dx.doi.org/10.1097/01376517-200710000-00005] [PMID: 17966295] 
[88] 
Bliss TM, Andres RH, Steinberg GK. Optimizing the success of cell transplantation therapy for stroke. Neurobiol Dis  2010; 37(2): 275-83.
[http://dx.doi.org/10.1016/j.nbd.2009.10.003] [PMID: 19822211] 
[89] 
Singh M, Pandey PK, Bhasin A, Padma MV, Mohanty S. Application of stem cells in stroke: A multifactorial approach. Front Neurosci  2020; 14: 473.
[http://dx.doi.org/10.3389/fnins.2020.00473] [PMID: 32581669] 
[90] 
Li Z, Dong X, Tian M, et al. Stem cell-based therapies for ischemic stroke: A systematic review and meta-analysis of clinical trials. Stem Cell Res Ther  2020; 11(1): 252.
[http://dx.doi.org/10.1186/s13287-020-01762-z] [PMID: 32586371] 
[91] 
Baker EW, Kinder HA, West FD. Neural stem cell therapy for stroke: A multimechanistic approach to restoring neurological function. Brain Behav  2019; 9(3): e01214.
[http://dx.doi.org/10.1002/brb3.1214] [PMID: 30747485] 
[92] 
Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol  2005; 57(6): 874-82.
[http://dx.doi.org/10.1002/ana.20501] [PMID: 15929052] 
[93] 
Bliss T, Guzman R, Daadi M, Steinberg GK. Cell transplantation therapy for stroke. Stroke  2007; 38(2): 817-26.
[http://dx.doi.org/10.1161/01.STR.0000247888.25985.62] [PMID: 17261746] 
[94] 
Hollenbach JA, Oksenberg JR. The immunogenetics of multiple sclerosis: A comprehensive review. J Autoimmun  2015; 64: 13-25.
[http://dx.doi.org/10.1016/j.jaut.2015.06.010] [PMID: 26142251] 
[95] 
Muraro PA, Martin R, Mancardi GL, Nicholas R, Sormani MP, Saccardi R. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat Rev Neurol  2017; 13(7): 391-405.
[http://dx.doi.org/10.1038/nrneurol.2017.81] [PMID: 28621766] 
[96] 
Muraro PA, Douek DC, Packer A, et al. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med  2005; 201(5): 805-16.
[http://dx.doi.org/10.1084/jem.20041679] [PMID: 15738052] 
[97] 
Mancardi G, Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol  2008; 7(7): 626-36.
[http://dx.doi.org/10.1016/S1474-4422(08)70138-8] [PMID: 18565456] 
[98] 
Wang X, Kimbrel EA, Ijichi K, et al. Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis. Stem Cell Reports  2014; 3(1): 115-30.
[http://dx.doi.org/10.1016/j.stemcr.2014.04.020] [PMID: 25068126] 
[99] 
Rahim F, Arjmand B, Tirdad R, Saki Malehi A. Stem cell therapy for multiple sclerosis. Cochrane Database Syst Rev  2018; 2018(6): CD013049.
[100] 
Marzouni ET, Dorcheh SP, Nejad-Moghaddam A, et al. Adipose-derived mesenchymal stem cells ameliorate lung epithelial injury through mitigating of oxidative stress in mustard lung. Regen Med  2020; 15(7): 1861-76.
[http://dx.doi.org/10.2217/rme-2020-0051] [PMID: 32935623] 
[101] 
Llufriu S, Sepúlveda M, Blanco Y, et al. Randomized placebo-controlled phase II trial of autologous mesenchymal stem cells in multiple sclerosis. PLoS One  2014; 9(12): e113936.
[http://dx.doi.org/10.1371/journal.pone.0113936] [PMID: 25436769] 
[102] 
Rockne RC, Adhikarla V, Tsaturyan L, et al. Long-term stability and computational analysis of migration patterns of L-MYC immortalized neural stem cells in the brain. PLoS One  2018; 13(8): e0199967.
[http://dx.doi.org/10.1371/journal.pone.0199967] [PMID: 30071048] 
[103] 
Harris VK, Stark J, Vyshkina T, et al. Phase I trial of intrathecal mesenchymal stem cell-derived neural progenitors in progressive multiple sclerosis. EBioMedicine  2018; 29: 23-30.
[http://dx.doi.org/10.1016/j.ebiom.2018.02.002] [PMID: 29449193] 
[104] 
Trounson A, McDonald C. Stem cell therapies in clinical trials: Progress and challenges. Cell Stem Cell  2015; 17(1): 11-22.
[http://dx.doi.org/10.1016/j.stem.2015.06.007] [PMID: 26140604] 
[105] 
Colpo GD, Furr Stimming E, Teixeira AL. Stem cells in animal models of Huntington disease: A systematic review. Mol Cell Neurosci  2019; 95: 43-50.
[http://dx.doi.org/10.1016/j.mcn.2019.01.006] [PMID: 30685323] 
[106] 
Dunnett SB, Rosser AE. Cell therapy in Huntington’s disease. NeuroRx  2004; 1(4): 394-405.
[http://dx.doi.org/10.1602/neurorx.1.4.394] [PMID: 15717043] 
[107] 
McColgan P, Tabrizi SJ. Huntington’s disease: A clinical review. Eur J Neurol  2018; 25(1): 24-34.
[http://dx.doi.org/10.1111/ene.13413] [PMID: 28817209] 
[108] 
Wild EJ, Tabrizi SJ. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol  2017; 16(10): 837-47.
[http://dx.doi.org/10.1016/S1474-4422(17)30280-6] [PMID: 28920889] 
[109] 
Connor B. Concise review: The use of stem cells for understanding and treating Huntington’s disease. Stem Cells  2018; 36(2): 146-60.
[http://dx.doi.org/10.1002/stem.2747] [PMID: 29178352] 
[110] 
Choi KA, Choi Y, Hong S. Stem cell transplantation for Huntington’s diseases. Methods  2018; 133: 104-12.
[http://dx.doi.org/10.1016/j.ymeth.2017.08.017] [PMID: 28867501] 
[111] 
Maucksch C, Vazey EM, Gordon RJ, Connor B. Stem cell-based therapy for Huntington’s disease. J Cell Biochem  2013; 114(4): 754-63.
[http://dx.doi.org/10.1002/jcb.24432] [PMID: 23097329] 
[112] 
Jeon I, Lee N, Li JY, et al. Neuronal properties, in vivo effects, and pathology of a Huntington’s disease patient-derived induced pluripotent stem cells. Stem Cells  2012; 30(9): 2054-62.
[http://dx.doi.org/10.1002/stem.1135] [PMID: 22628015] 
[113] 
Cohen-Carmon D, Sorek M, Lerner V, et al. Progerin-induced transcriptional changes in Huntington’s disease human pluripotent stem cell-derived neurons. Mol Neurobiol  2020; 57(3): 1768-77.
[http://dx.doi.org/10.1007/s12035-019-01839-8] [PMID: 31834602] 
[114] 
Clelland CD, Barker RA, Watts C. Cell therapy in Huntington disease. Neurosurg Focus  2008; 24(3-4): E9.
[http://dx.doi.org/10.3171/FOC/2008/24/3-4/E8] [PMID: 18341412] 
[115] 
Cho IK, Hunter CE, Ye S, Pongos AL, Chan AWS. Combination of stem cell and gene therapy ameliorates symptoms in Huntington’s disease mice. NPJ Regen Med  2019; 4(1): 7.
[http://dx.doi.org/10.1038/s41536-019-0066-7] [PMID: 30937182] 
[116] 
Im W, Lee S-T, Chu K, Kim M, Roh J-K. Stem cells transplantation and Huntington’s disease. Int J Stem Cells  2009; 2(2): 102-8.
[http://dx.doi.org/10.15283/ijsc.2009.2.2.102] [PMID: 24855528] 
[117] 
Romano G. Stem cell transplantation therapy: Controversy over ethical issues and clinical relevance. Drug News Perspect  2004; 17(10): 637-45.
[http://dx.doi.org/10.1358/dnp.2004.17.10.873915] [PMID: 15696228] 
[118] 
Feng Z, Gao F. Stem cell challenges in the treatment of neurodegenerative disease. CNS Neurosci Ther  2012; 18(2): 142-8.
[http://dx.doi.org/10.1111/j.1755-5949.2011.00239.x] [PMID: 22070610] 
[119] 
Rusu E, Necula LG, Neagu AI, et al. Current status of stem cell therapy: Opportunities and limitations. Turk J Biol  2016; 40(5): 955-67.
[http://dx.doi.org/10.3906/biy-1506-95] 
[120] 
Schwarz SC, Schwarz J. Translation of stem cell therapy for neurological diseases. Transl Res  2010; 156(3): 155-60.
[http://dx.doi.org/10.1016/j.trsl.2010.07.002] [PMID: 20801412] 
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DOI https://dx.doi.org/10.2174/1574888X16666210810103838	Print ISSN 1574-888X
Publisher Name Bentham Science Publisher	Online ISSN 2212-3946
Current Stem Cell Research & Therapy

Exploring the Role of Stem Cell Therapy in Treating Neurodegenerative Diseases: Challenges and Current Perspectives

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