Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2015, Vol. 6 Issue (6) : 499-503     DOI: 10.14336/AD.2014.1201
Review Article |
Cell Therapy for Parkinson’s Disease: New Hope from Reprogramming Technologies
Chen Zhiguo1,2,3,*()
1 Cell Therapy Center, Xuanwu Hospital, Capital Medical University, and Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, 100053, China
2 Center of Neural Injury and Repair, Beijing Institute for Brain Disorders, Beijing, China
3 Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China
Download: PDF(718 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Parkinson’s disease (PD) is a neurodegenerative disease with the major pathology being the progressive loss of dopaminergic (DA) midbrain neurons in the substantia nigra. As early as in the 1980s, open-label clinical trials employing fetal ventral mesencephalon (fVM) tissues have demonstrated significant efficacy for PD treatment, which led to two NIH-sponsored double-blind placebo-controlled clinical trials. However, both trials showed only mild outcome. Retrospective analysis revealed several possible reasons that include patient selection, heterogeneity of grafts, immune recognition of grafts, lack of standardization of transplantation procedure and uneven distribution of grafts. Recent years have seen advances in reprogramming technologies which may provide solutions to the problems associated with fVM tissues. Induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) hold promise for generating clinical grade DA neural cells that are safe, homogeneous, scalable and standardizable. These new technologies may bring back clinical trials using cell therapy for PD treatment in the future.

Keywords cell therapy      Parkinson’s disease      reprogramming      dopaminergic neurons      clinical trials     
Corresponding Authors: Chen Zhiguo     E-mail: chenzhiguo@gmail.com
About author:

present address: Kunming Biomed International, Kunming, Yunnan, 650500, China

Issue Date: 01 December 2015
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Chen Zhiguo
Cite this article:   
Chen Zhiguo. Cell Therapy for Parkinson’s Disease: New Hope from Reprogramming Technologies[J]. Aging and disease, 2015, 6(6): 499-503.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2014.1201     OR     http://www.aginganddisease.org/EN/Y2015/V6/I6/499
[1] Buttery PC, Barker RA (2014). Treating Parkinson's disease in the 21st century: can stem cell transplantation compete? J Comp Neurol, 522: 2802-2816
[2] Williams-Gray CH, Evans JR, Goris A, Foltynie T, Ban M, Robbins TW,et al. (2009). The distinct cognitive syndromes of Parkinson's disease: 5 year follow-up of the CamPaIGN cohort. Brain, 132: 2958-2969
[3] Chaudhuri KR, Healy DG, Schapira AH (2006). Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol, 5: 235-245
[4] Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA,et al. (2007). Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet, 369: 2097-2105
[5] Marks WJ, Jr., Ostrem JL, Verhagen L, Starr PA, Larson PS, Bakay RA,et al. (2008). Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson's disease: an open-label, phase I trial. Lancet Neurol, 7: 400-408
[6] Marks WJ Jr., Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N,et al. (2010). Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol, 9: 1164-1172
[7] Bankiewicz KS, Forsayeth J, Eberling JL, Sanchez-Pernaute R, Pivirotto P, Bringas J,et al. (2006). Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol Ther, 14: 564-570
[8] Azzouz M, Martin-Rendon E, Barber RD, Mitrophanous KA, Carter EE, Rohll JB,et al. (2002). Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson's disease. J Neurosci, 22: 10302-10312
[9] Jarraya B, Boulet S, Ralph GS, Jan C, Bonvento G, Azzouz M,et al. (2009). Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia. Sci Transl Med, 1: 2ra4
[10] Arjona V, Minguez-Castellanos A, Montoro RJ, Ortega A, Escamilla F, Toledo-Aral JJ,et al. (2003). Autotransplantation of human carotid body cell aggregates for treatment of Parkinson's disease. Neurosurgery, 53: 321-328; discussion 328-330
[11] Backlund EO, Granberg PO, Hamberger B, Knutsson E, Martensson A, Sedvall G,et al. (1985). Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials. J Neurosurg, 62: 169-173
[12] Itakura T, Uematsu Y, Nakao N, Nakai E, Nakai K (1997). Transplantation of autologous sympathetic ganglion into the brain with Parkinson's disease. Long-term follow-up of 35 cases. Stereotact Funct Neurosurg, 69: 112-115
[13] Schumacher JM, Ellias SA, Palmer EP, Kott HS, Dinsmore J, Dempsey PK,et al. (2000). Transplantation of embryonic porcine mesencephalic tissue in patients with PD. Neurology, 54: 1042-1050
[14] Lindvall O, Brundin P, Widner H, Rehncrona S, Gustavii B, Frackowiak R,et al. (1990). Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. Science, 247: 574-577
[15] Hagell P, Schrag A, Piccini P, Jahanshahi M, Brown R, Rehncrona S,et al. (1999). Sequential bilateral transplantation in Parkinson's disease: effects of the second graft. Brain, 122( Pt 6): 1121-1132
[16] Mendez I, Vinuela A, Astradsson A, Mukhida K, Hallett P, Robertson H,et al. (2008). Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nat Med, 14: 507-509
[17] Piccini P, Brooks DJ, Bjorklund A, Gunn RN, Grasby PM, Rimoldi O,et al. (1999). Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient. Nat Neurosci, 2: 1137-1140
[18] Wenning GK, Odin P, Morrish P, Rehncrona S, Widner H, Brundin P,et al. (1997). Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease. Ann Neurol, 42: 95-107
[19] Remy P, Samson Y, Hantraye P, Fontaine A, Defer G, Mangin JF,et al. (1995). Clinical correlates of [18F]fluorodopa uptake in five grafted parkinsonian patients. Ann Neurol, 38: 580-588
[20] Widner H, Tetrud J, Rehncrona S, Snow B, Brundin P, Gustavii B,et al. (1992). Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). N Engl J Med, 327: 1556-1563
[21] Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF,et al. (2003). A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol, 54: 403-414
[22] Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R,et al. (2001). Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med, 344: 710-719
[23] Ma Y, Tang C, Chaly T, Greene P, Breeze R, Fahn S,et al. (2010). Dopamine cell implantation in Parkinson's disease: long-term clinical and (18)F-FDOPA PET outcomes. J Nucl Med, 51: 7-15
[24] Politis M, Lindvall O (2012). Clinical application of stem cell therapy in Parkinson's disease. BMC Med, 10: 1
[25] Chen Z, Palmer TD (2008). Cellular repair of CNS disorders: an immunological perspective. Hum Mol Genet, 17: R84-92
[26] Chen Z, Phillips LK, Gould E, Campisi J, Lee SW, Ormerod BK,et al. (2011). MHC mismatch inhibits neurogenesis and neuron maturation in stem cell allografts. PLoS One, 6: e14787
[27] Chen Z, Palmer TD (2013). Differential roles of TNFR1 and TNFR2 signaling in adult hippocampal neurogenesis. Brain Behav Immun, 30: 45-53
[28] Shin E, Tronci E, Carta M (2012). Role of Serotonin Neurons in L-DOPA- and Graft-Induced Dyskinesia in a Rat Model of Parkinson's Disease. Parkinsons Dis, 2012: 370190
[29] Petit GH, Olsson TT, Brundin P (2014). The future of cell therapies and brain repair: Parkinson's disease leads the way. Neuropathol Appl Neurobiol, 40: 60-70
[30] Takahashi K, Yamanaka S (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126: 663-676
[31] Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K,et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131: 861-872
[32] Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K (2009). Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature, 458: 771-775
[33] Okita K, Hong H, Takahashi K, Yamanaka S (2010). Generation of mouse-induced pluripotent stem cells with plasmid vectors. Nat Protoc, 5: 418-428
[34] Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG,et al. (2009). Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell, 136: 964-977
[35] Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K (2008). Induced pluripotent stem cells generated without viral integration. Science, 322: 945-949
[36] Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R,et al. (2009). piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature, 458: 766-770
[37] Hou P, Li Y, Zhang X, Liu C, Guan J, Li H,et al. (2013). Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science, 341: 651-654
[38] Dowey SN, Huang X, Chou BK, Ye Z, Cheng L (2012). Generation of integration-free human induced pluripotent stem cells from postnatal blood mononuclear cells by plasmid vector expression. Nat Protoc, 7: 2013-2021
[39] Pruszak J, Sonntag KC, Aung MH, Sanchez-Pernaute R, Isacson O (2007). Markers and methods for cell sorting of human embryonic stem cell-derived neural cell populations. Stem Cells, 25: 2257-2268
[40] Jonsson ME, Ono Y, Bjorklund A, Thompson LH (2009). Identification of transplantable dopamine neuron precursors at different stages of midbrain neurogenesis. Exp Neurol, 219: 341-354
[41] Xi J, Liu Y, Liu H, Chen H, Emborg ME, Zhang SC (2012). Specification of midbrain dopamine neurons from primate pluripotent stem cells. Stem Cells, 30: 1655-1663
[42] Chung S, Moon JI, Leung A, Aldrich D, Lukianov S, Kitayama Y,et al. (2011). ES cell-derived renewable and functional midbrain dopaminergic progenitors. Proc Natl Acad Sci U S A, 108: 9703-9708
[43] Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC, Wernig M (2010). Direct conversion of fibroblasts to functional neurons by defined factors. Nature, 463: 1035-1041
[44] Sheng C, Zheng Q, Wu J, Xu Z, Sang L, Wang L,et al. (2012). Generation of dopaminergic neurons directly from mouse fibroblasts and fibroblast-derived neural progenitors. Cell Res, 22: 769-772
[45] Caiazzo M, Dell'Anno MT, Dvoretskova E, Lazarevic D, Taverna S, Leo D,et al. (2011). Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature, 476: 224-227
[46] Liu X, Li F, Stubblefield EA, Blanchard B, Richards TL, Larson GA,et al. (2012). Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Res, 22: 321-332
[47] Liu X, Huang Q, Li F, Li CY (2014). Enhancing the efficiency of direct reprogramming of human primary fibroblasts into dopaminergic neuron-like cells through p53 suppression. Sci China Life Sci, 57: 867-875
[48] Pfisterer U, Kirkeby A, Torper O, Wood J, Nelander J, Dufour A,et al. (2011). Direct conversion of human fibroblasts to dopaminergic neurons. Proc Natl Acad Sci U S A, 108: 10343-10348
[49] Sheng C, Zheng Q, Wu J, Xu Z, Wang L, Li W,et al. (2012). Direct reprogramming of Sertoli cells into multipotent neural stem cells by defined factors. Cell Res, 22: 208-218
[50] Wu J, Sheng C, Liu Z, Jia W, Wang B, Li M,et al. (2015). Lmx1a enhances the effect of iNSCs in a PD model. Stem Cell Res, 14: 1-9
[51] Lujan E, Chanda S, Ahlenius H, Sudhof TC, Wernig M (2012). Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proc Natl Acad Sci U S A, 109: 2527-2532
[52] Kim SM, Flasskamp H, Hermann A, Arauzo-Bravo MJ, Lee SC, Lee SH,et al. (2014). Direct conversion of mouse fibroblasts into induced neural stem cells. Nat Protoc, 9: 871-881
[53] Kim J, Efe JA, Zhu S, Talantova M, Yuan X, Wang S,et al. (2011). Direct reprogramming of mouse fibroblasts to neural progenitors. Proc Natl Acad Sci U S A, 108: 7838-7843
[54] Wang L, Huang W, Su H, Xue Y, Su Z, Liao B,et al. (2013). Generation of integration-free neural progenitor cells from cells in human urine. Nat Methods, 10: 84-89
[55] Thier M, Worsdorfer P, Lakes YB, Gorris R, Herms S, Opitz T,et al. (2012). Direct conversion of fibroblasts into stably expandable neural stem cells. Cell Stem Cell, 10: 473-479
[56] Han DW, Tapia N, Hermann A, Hemmer K, Hoing S, Arauzo-Bravo MJ,et al. (2012). Direct reprogramming of fibroblasts into neural stem cells by defined factors. Cell Stem Cell, 10: 465-472
[1] Ashok K. Shetty, Maheedhar Kodali, Raghavendra Upadhya, Leelavathi N. Madhu. Emerging Anti-Aging Strategies - Scientific Basis and Efficacy[J]. Aging and disease, 2018, 9(6): 1165-1184.
[2] Yong-Fei Zhao, Qiong Zhang, Jian-Feng Zhang, Zhi-Yin Lou, Hen-Bing Zu, Zi-Gao Wang, Wei-Cheng Zeng, Kai Yao, Bao-Guo Xiao. The Synergy of Aging and LPS Exposure in a Mouse Model of Parkinson’s Disease[J]. Aging and disease, 2018, 9(5): 785-797.
[3] De Lazzari Federica, Bubacco Luigi, Whitworth Alexander J, Bisaglia Marco. Superoxide Radical Dismutation as New Therapeutic Strategy in Parkinson’s Disease[J]. Aging and disease, 2018, 9(4): 716-728.
[4] Zhang Li, Hao Junwei, Zheng Yan, Su Ruijun, Liao Yajin, Gong Xiaoli, Liu Limin, Wang Xiaomin. Fucoidan Protects Dopaminergic Neurons by Enhancing the Mitochondrial Function in a Rotenone-induced Rat Model of Parkinson’s Disease[J]. Aging and disease, 2018, 9(4): 590-604.
[5] Perez-Roca Laia, Adame-Castillo Cristina, Campdelacreu Jaume, Ispierto Lourdes, Vilas Dolores, Rene Ramon, Alvarez Ramiro, Gascon-Bayarri Jordi, Serrano-Munoz Maria A., Ariza Aurelio, Beyer Katrin. Glucocerebrosidase mRNA is Diminished in Brain of Lewy Body Diseases and Changes with Disease Progression in Blood[J]. Aging and disease, 2018, 9(2): 208-219.
[6] Zhang Meng, Deng Yong-Ning, Zhang Jing-Yi, Liu Jie, Li Yan-Bo, Su Hua, Qu Qiu-Min. SIRT3 Protects Rotenone-induced Injury in SH-SY5Y Cells by Promoting Autophagy through the LKB1-AMPK-mTOR Pathway[J]. Aging and disease, 2018, 9(2): 273-286.
[7] Sun Qian, Wang Tian, Jiang Tian-Fang, Huang Pei, Wang Ying, Xiao Qin, Liu Jun, Chen Sheng-Di. Clinical Profile of Chinese Long-Term Parkinson’s Disease Survivors With 10 Years of Disease Duration and Beyond[J]. Aging and disease, 2018, 9(1): 8-16.
[8] Cao Yiwei, Wang Rui-Hong. Associations among Metabolism, Circadian Rhythm and Age-Associated Diseases[J]. Aging and disease, 2017, 8(3): 314-333.
[9] Lv Deyong, Li Jingbo, Li Hongfu, Fu Yu, Wang Wei. Imaging and Quantitative Analysis of the Interstitial Space in the Caudate Nucleus in a Rotenone-Induced Rat Model of Parkinson’s Disease Using Tracer-based MRI[J]. Aging and disease, 2017, 8(1): 1-6.
[10] Su Ruijun, Sun Min, Wang Wei, Zhang Jianliang, Zhang Li, Zhen Junli, Qian Yanjing, Zheng Yan, Wang Xiaomin. A Novel Immunosuppressor, (5R)-5-Hydroxytriptolide, Alleviates Movement Disorder and Neuroinflammation in a 6-OHDA Hemiparkinsonian Rat Model[J]. Aging and disease, 2017, 8(1): 31-43.
[11] Smirnova Natalya A., Kaidery Navneet Ammal, Hushpulian Dmitry M., Rakhman Ilay I., Poloznikov Andrey A., Tishkov Vladimir I., Karuppagounder Saravanan S., Gaisina Irina N., Pekcec Anton, Leyen Klaus Van, Kazakov Sergey V., Yang Lichuan, Thomas Bobby, Ratan Rajiv R., Gazaryan Irina G.. Bioactive Flavonoids and Catechols as Hif1 and Nrf2 Protein Stabilizers - Implications for Parkinson’s Disease[J]. Aging and disease, 2016, 7(6): 745-762.
[12] Sun Qian, Wang Tian, Jiang Tian-Fang, Huang Pei, Li Dun-Hui, Wang Ying, Xiao Qin, Liu Jun, Chen Sheng-Di. Effect of a Leucine-rich Repeat Kinase 2 Variant on Motor and Non-motor Symptoms in Chinese Parkinson’s Disease Patients[J]. Aging and disease, 2016, 7(3): 230-236.
[13] Claassen Daniel O., Dobolyi David G., Isaacs David A., Roman Olivia C., Herb Joshua, Wylie Scott A., Neimat Joseph S., Donahue Manus J., Hedera Peter, Zald David H., Landman Bennett A., Bowman Aaron B., Dawant Benoit M., Rane Swati. Linear and Curvilinear Trajectories of Cortical Loss with Advancing Age and Disease Duration in Parkinson’s Disease[J]. Aging and disease, 2016, 7(3): 220-229.
[14] Sterling Nicholas W., Lichtenstein Maya, Lee Eun-Young, Lewis Mechelle M., Evans Alicia, Eslinger Paul J., Du Guangwei, Gao Xiang, Chen Honglei, Kong Lan, Huang Xuemei. Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson’s Disease[J]. Aging and disease, 2016, 7(3): 237-245.
[15] Yalcin Ahmet, Atmis Volkan, Karaarslan Cengiz Ozlem, Cinar Esat, Aras Sevgi, Varli Murat, Atli Teslime. Evaluation of Cardiac Autonomic Functions in Older Parkinson’s Disease Patients: a Cross-Sectional Study[J]. Aging and disease, 2016, 7(1): 28-35.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd