Use of genetically altered stem cells for the treatment of Huntington's disease

Brain Sciences

Volumn 4, Issue 1, 2014, Pages 202-219

  Crane, Andrew T ^a   Rossignol, Julien ^a,b   Dunbar, Gary L ^a,c  

^a CENTRAL MICHIGAN UNIVERSITY   (United States)

^b Children's Hospital of Michigan   (United States)

^c Field Neurosciences Institute   (United States)

Author keywords

Brain derived neurotrophic factor; Cell therapy; Genetic engineering; Huntington's disease; Induced pluripotent stem cells; Mesenchymal stem cells

Indexed keywords

ADENOVIRUS VECTOR; BRAIN DERIVED NEUROTROPHIC FACTOR; FIBROBLAST GROWTH FACTOR; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; HUNTINGTIN; NERVE GROWTH FACTOR; OCTAMER TRANSCRIPTION FACTOR 4; TRANSCRIPTION FACTOR SOX2;

CELL ENGINEERING; DISEASE MODEL; FETUS CELL; GENE THERAPY; GENETIC ENGINEERING; HUMAN; HUNTINGTON CHOREA; MESENCHYMAL STEM CELL; NONHUMAN; PLURIPOTENT STEM CELL; REVIEW; RNA INTERFERENCE; STEM CELL; STEM CELL TRANSPLANTATION;

EID: 84949517436     PISSN: None     EISSN: 20763425     Source Type: Journal    
DOI: 10.3390/brainsci4010202     Document Type: Review

References (77)

1. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 1993, 72, 971-983.
2. Zuccato, C.; Valenza, M.; Cattaneo, E. Molecular mechanisms and potential therapeutical targets in Huntington's disease. Physiol. Rev. 2010, 90, 905-981.
3. Aylward, E.H.; Sparks, B.F.; Field, K.M.; Yallapragada, V.; Shpritz, B.D.; Rosenblatt, A.; Brandt, J.; Gourley, L.M.; Liang, K.; Zhou, H.; et al. Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology 2004, 63, 66-72.
4. Tabrizi, S.J.; Langbehn, D.R.; Leavitt, B.R.; Roos, R.A.; Durr, A.; Craufurd, D.; Kennard, C.; Hicks, S.L.; Fox, N.C.; Scahill, R.I.; et al. TRACK-HD investigators Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: Cross-sectional analysis of baseline data. Lancet Neurol. 2009, 8, 791-801.
5. Vonsattel, J.P.; Myers, R.H.; Stevens, T.J.; Ferrante, R.J.; Bird, E.D.; Richardson, E.P., Jr. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 1985, 44, 559-577.
6. Glass, M.; Dragunow, M.; Faull, R.L. The pattern of neurodegeneration in Huntington's disease: A comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington's disease. Neuroscience 2000, 97, 505-519
7. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: A randomized controlled trial. Neurology 2006, 66, 366-372.
8. Shoulson, I.; Young, A.B. Milestones in Huntington disease. Mov. Disord. 2011, 26, 1127-1133
9. Baquet, Z.C.; Gorski, J.A.; Jones, K.R. Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain-derived neurotrophic factor. J. Neurosci. 2004, 24, 4250-4258.
10. Zuccato, C.; Marullo, M.; Conforti, P.; MacDonald, M.E.; Tartari, M.; Cattaneo, E. Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington's disease. Brain Pathol. 2008, 18, 225-238.
11. Altar, C.A.; Cai, N.; Bliven, T.; Juhasz, M.; Conner, J.M.; Acheson, A.L.; Lindsay, R.M.; Wiegand, S.J. Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 1997, 389, 856-860.
12. Ivkovic, S.; Polonskaia, O.; Fariñas, I.; Ehrlich, M.E. Brain-derived neurotrophic factor regulates maturation of the DARPP-32 phenotype in striatal medium spiny neurons: Studies in vivo and in vitro. Neuroscience 1997, 79, 509-516.
13. Canals, J.M.; Pineda, J.R.; Torres-Peraza, J.F.; Bosch, M.; Martín-Ibañez, R.; Muñoz, M.T.; Mengod, G.; Ernfors, P.; Alberch, J. Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. J. Neurosci. 2004, 24, 7727-7739.
14. Gharami, K.; Xie, Y.; An, J.J.; Tonegawa, S.; Xu, B. Brain-derived neurotrophic factor over-expression in the forebrain ameliorates Huntington's disease phenotypes in mice. J. Neurochem. 2008, 105, 369-379.
15. Xie, Y.; Hayden, M.R.; Xu, B. BDNF overexpression in the forebrain rescues Huntington's disease phenotypes in YAC128 mice. J. Neurosci. 2010, 30, 14708-14718.
16. Jin, K.; LaFevre-Bernt, M.; Sun, Y.; Chen, S.; Gafni, J.; Crippen, D.; Logvinova, A.; Ross, C.A.; Greenberg, D.A.; Ellerby, L.M. FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington's disease. Proc. Natl. Acad. Sci. USA 2005, 102, 18189-18194.
17. Pardridge, W.M. Blood-brain barrier delivery. Drug Discov. Today 2007, 12, 54-61.
18. Bemelmans, A.P.; Horellou, P.; Pradier, L.; Brunet, I.; Colin, P.; Mallet, J. 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, 10, 2987-2997.
19. Kells, A.P.; Fong, D.M.; Dragunow, M.; During, M.J.; Young, D.; Connor, B. AAV-mediated gene delivery of BDNF or GDNF is neuroprotective in a model of Huntington disease. Mol. Ther. 2004, 9, 682-688.
20. Chmielnicki, E.; Benraiss, A.; Economides, A.N.; Goldman, S.A. Adenovirally expressed noggin and brain-derived neurotrophic factor cooperate to induce new medium spiny neurons from resident progenitor cells in the adult striatal ventricular zone. J. Neurosci. 2004, 24, 2133-2142.
21. Benraiss, A.; Toner, M.J.; Xu, Q.; Bruel-Jungerman, E.; Rogers, E.H.; Wang, F.; Economides, A.N.; Davidson, B.L.; Kageyama, R.; Nedergaard, M.; et al. Sustained mobilization of endogenous neural progenitors delays disease progression in a transgenic model of Huntington's disease. Cell Stem Cell 2013, 12, 787-799.
22. Cho, S.-R.; Benraiss, A.; Chmielnicki, E.; Samdani, A.; Economides, A.; Goldman, S.A. Induction of neostriatal neurogenesis slows disease progression in a transgenic murine model of Huntington disease. J. Clin. Investig. 2007, 117, 2889-2902.
23. Benraiss, A.; Bruel-Jungerman, E.; Lu, G.; Economides, A.N.; Davidson, B.; Goldman, S.A. Sustained induction of neuronal addition to the adult rat neostriatum by AAV4-delivered noggin and BDNF. Gene Ther. 2012, 19, 483-493.
24. Friedenstein, A.J.; Gorskaja, J.F.; Kulagina, N.N. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp. Hematol. 1976, 4, 267-274.
25. Ahmadbeigi, N.; Soleimani, M.; Gheisari, Y.; Vasei, M.; Amanpour, S.; Bagherizadeh, I.; Shariati, S.A.M.; Azadmanesh, K.; Amini, S.; Shafiee, A.; et al. Dormant phase and multinuclear cells: Two key phenomena in early culture of murine bone marrow mesenchymal stem cells. Stem Cells Dev. 2011, 20, 1337-1347.
26. Lescaudron, L.; Unni, D.; Dunbar, G.L. Autologous adult bone marrow stem cell transplantation in an animal model of Huntington's disease: Behavioral and morphological outcomes. Int. J. Neurosci. 2003, 113, 945-956.
27. Bantubungi, K.; Blum, D.; Cuvelier, L.; Wislet-Gendebien, S.; Rogister, B.; Brouillet, E.; Schiffmann, S.N. Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease. Mol. Cell. Neurosci. 2008, 37, 454-470.
28. Rossignol, J.; Boyer, C.; Lévèque, X.; Fink, K.D.; Thinard, R.; Blanchard, F.; Dunbar, G.L.; Lescaudron, L. Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease: Morphological and behavioral outcomes. Behav. Brain Res. 2011, 217, 369-378.
29. Lin, Y.-T.; Chern, Y.; Shen, C.-K.J.; Wen, H.-L.; Chang, Y.-C.; Li, H.; Cheng, T.-H.; Hsieh-Li, H.M. Human mesenchymal stem cells prolong survival and ameliorate motor deficit through trophic support in Huntington's disease mouse models. PLoS One 2011, 6, e22924.
30. Rossignol, J.; Boyer, C.; Thinard, R.; Remy, S.; Dugast, A.-S.; Dubayle, D.; Dey, N.D.; Boeffard, F.; Delecrin, J.; Heymann, D.; et al. Mesenchymal stem cells induce a weak immune response in the rat striatum after allo or xenotransplantation. J. Cell. Mol. Med. 2009, 13, 2547-2558.
31. Griffin, M.D.; Ritter, T.; Mahon, B.P. Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum. Gene Ther. 2010, 21, 1641-1655.
32. Shi, Y.; Su, J.; Roberts, A.I.; Shou, P.; Rabson, A.B.; Ren, G. How mesenchymal stem cells interact with tissue immune responses. Trends Immunol. 2012, 33, 136-143.
33. Engela, A.U.; Baan, C.C.; Dor, F.J.; Weimar, W.; Hoogduijn, M.J. On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation. Front. Immunol. 2012, 3, 126.
34. Crigler, L.; Robey, R.C.; Asawachaicharn, A.; Gaupp, D.; Phinney, D.G. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp. Neurol. 2006, 198, 54-64.
35. Drago, D.; Cossetti, C.; Iraci, N.; Gaude, E.; Musco, G.; Bachi, A.; Pluchino, S. The stem cell secretome and its role in brain repair. Biochimie 2013, 95, 2271-2285.
36. Sadan, O.; Shemesh, N.; Barzilay, R.; Dadon-Nahum, M.; Blumenfeld-Katzir, T.; Assaf, Y.; Yeshurun, M.; Djaldetti, R.; Cohen, Y.; Melamed, E.; et al. Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington's disease. Exp. Neurol. 2012, 234, 417-427.
37. Sadan, O.; Melamed, E.; Offen, D. Intrastriatal transplantation of neurotrophic factor-secreting human mesenchymal stem cells improves motor function and extends survival in R6/2 transgenic mouse model for Huntington's disease. PLoS Curr. 2012, 4, doi:10.1371/4f7f6dc013d4e.
38. Pérez-Navarro, E.; Canudas, A.M.; Akerund, P.; Alberch, J.; Arenas, E. 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, 75, 2190-2199.
39. Giralt, A.; Friedman, H.C.; Caneda-Ferrón, B.; Urbán, N.; Moreno, E.; Rubio, N.; Blanco, J.; Peterson, A.; Canals, J.M.; Alberch, J. BDNF regulation under GFAP promoter provides engineered astrocytes as a new approach for long-term protection in Huntington's disease. Gene Ther. 2010, 17, 1294-1308.
40. Dey, N.D.; Bombard, M.C.; Roland, B.P.; Davidson, S.; Lu, M.; Rossignol, J.; Sandstrom, M.I.; Skeel, R.L.; Lescaudron, L.; Dunbar, G.L. Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington's disease. Behav. Brain Res. 2010, 214, 193-200.
41. Bauer, G.; Dao, M.A.; Case, S.S.; Meyerrose, T.; Wirthlin, L.; Zhou, P.; Wang, X.; Herrbrich, P.; Arevalo, J.; Csik, S.; et al. In vivo biosafety model to assess the risk of adverse events from retroviral and lentiviral vectors. Mol. Ther. 2008, 16, 1308-1315.
42. Duyao, M.P.; Auerbach, A.B.; Ryan, A.; Persichetti, F.; Barnes, G.T.; McNeil, S.M.; Ge, P.; Vonsattel, J.P.; Gusella, J.F.; Joyner, A.L. Inactivation of the mouse Huntington's disease gene homolog HDH. Science 1995, 269, 407-410.
43. Dragatsis, I.; Levine, M.S.; Zeitlin, S. Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nat. Genet. 2000, 26, 300-306.
44. Qin, Z.-H.; Wang, Y.; Sapp, E.; Cuiffo, B.; Wanker, E.; Hayden, M.R.; Kegel, K.B.; Aronin, N.; DiFiglia, M. Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction. J. Neurosci. 2004, 24, 269-281.
45. Southwell, A.L.; Khoshnan, A.; Dunn, D.E.; Bugg, C.W.; Lo, D.C.; Patterson, P.H. Intrabodies binding the proline-rich domains of mutant huntingtin increase its turnover and reduce neurotoxicity. J. Neurosci. 2008, 28, 9013-9020.
46. Wang, C.-E.; Zhou, H.; McGuire, J.R.; Cerullo, V.; Lee, B.; Li, S.-H.; Li, X.-J. Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin. J. Cell Biol. 2008, 181, 803-816.
47. Southwell, A.L.; Bugg, C.W.; Kaltenbach, L.S.; Dunn, D.; Butland, S.; Weiss, A.; Paganetti, P.; Lo, D.C.; Patterson, P.H. Perturbation with intrabodies reveals that calpain cleavage is required for degradation of huntingtin exon 1. PLoS One 2011, 6, e16676.
48. Butler, D.C.; McLear, J.A.; Messer, A. Engineered antibody therapies to counteract mutant huntingtin and related toxic intracellular proteins. Prog. Neurobiol. 2012, 97, 190-204.
49. Harper, S.Q.; Staber, P.D.; He, X.; Eliason, S.L.; Martins, I.H.; Mao, Q.; Yang, L.; Kotin, R.M.; Paulson, H.L.; Davidson, B.L. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc. Natl. Acad. Sci. USA 2005, 102, 5820-5825.
50. Rodriguez-Lebron, E.; Denovan-Wright, E.M.; Nash, K.; Lewin, A.S.; Mandel, R.J. Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice. Mol. Ther. 2005, 12, 618-633.
51. DiFiglia, M.; Sena-Esteves, M.; Chase, K.; Sapp, E.; Pfister, E.; Sass, M.; Yoder, J.; Reeves, P.; Pandey, R.K.; Rajeev, K.G.; et al. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc. Natl. Acad. Sci. USA 2007, 104, 17204-17209.
52. McBride, J.L.; Pitzer, M.R.; Boudreau, R.L.; Dufour, B.; Hobbs, T.; Ojeda, S.R.; Davidson, B.L. Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington's disease. Mol. Ther. 2011, 19, 2152-2162.
53. Wang, Y.-L.; Liu, W.; Wada, E.; Murata, M.; Wada, K.; Kanazawa, I. Clinico-pathological rescue of a model mouse of Huntington's disease by siRNA. Neurosci. Res. 2005, 53, 241-249.
54. Spees, J.L.; Olson, S.D.; Whitney, M.J.; Prockop, D.J. Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl. Acad. Sci. USA 2006, 103, 1283-1288.
55. Gerdes, H.-H.; Carvalho, R.N. Intercellular transfer mediated by tunneling nanotubes. Curr. Opin. Cell Biol. 2008, 20, 470-475.
56. Simons, M.; Raposo, G. Exosomes-vesicular carriers for intercellular communication. Curr. Opin. Cell Biol. 2009, 21, 575-581.
57. Gahan, P.B.; Stroun, M. The virtosome-a novel cytosolic informative entity and intercellular messenger. Cell Biochem. Funct. 2010, 28, 529-538.
58. Olson, S.D.; Kambal, A.; Pollock, K.; Mitchell, G.-M.; Stewart, H.; Kalomoiris, S.; Cary, W.; Nacey, C.; Pepper, K.; Nolta, J.A. Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin. Mol. Cell. Neurosci. 2012, 49, 271-281.
59. Nichols, J.; Zevnik, B.; Anastassiadis, K.; Niwa, H.; Klewe-Nebenius, D.; Chambers, I.; Schöler, H.; Smith, A. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 1998, 95, 379-391.
60. Avilion, A.A.; Nicolis, S.K.; Pevny, L.H.; Perez, L.; Vivian, N.; Lovell-Badge, R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev. 2003, 17, 126-140.
61. Bachoud-Lévi, A.C.; Rémy, P.; Nguyen, J.P.; Brugières, P.; Lefaucheur, J.P.; Bourdet, C.; Baudic, S.; Gaura, V.; Maison, P.; Haddad, B.; et al. Motor and cognitive improvements in patients with Huntington's disease after neural transplantation. Lancet 2000, 356, 1975-1979.
62. Bachoud-Lévi, A.-C.; Gaura, V.; Brugières, P.; Lefaucheur, J.-P.; Boissé, M.-F.; Maison, P.; Baudic, S.; Ribeiro, M.-J.; Bourdet, C.; Remy, P.; et al. Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: A long-term follow-up study. Lancet Neurol. 2006, 5, 303-309.
63. Bachoud-Lévi, A.-C. Neural grafts in Huntington's disease: Viability after 10 years. Lancet Neurol. 2009, 8, 979-981.
64. Reuter, S.; Grüner, B.; Buck, A.K.; Blumstein, N.; Kern, P.; Reske, S.N. Long-term follow-up of metabolic activity in human alveolar echinococcosis using FDG-PET. Nukl. Nucl. Med. 2008, 47, 147-152.
65. Cicchetti, F.; Saporta, S.; Hauser, R.A.; Parent, M.; Saint-Pierre, M.; Sanberg, P.R.; Li, X.J.; Parker, J.R.; Chu, Y.; Mufson, E.J.; et al. Neural transplants in patients with Huntington's disease undergo disease-like neuronal degeneration. Proc. Natl. Acad. Sci. USA 2009, 106, 12483-12488.
66. Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126, 663-676.
67. Juopperi, T.A.; Kim, W.R.; Chiang, C.-H.; Yu, H.; Margolis, R.L.; Ross, C.A.; Ming, G.; Song, H. Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington's disease patient cells. Mol. Brain 2012, 5, 17.
68. HD iPSC Consortium. Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell 2012, 11, 264-278.
69. Zhang, N.; An, M.C.; Montoro, D.; Ellerby, L.M. Characterization of Human Huntington's Disease Cell Model from Induced Pluripotent Stem Cells. PLoS Curr. 2010, 2, doi:10.1371/ currents.RRN1193.
70. An, M.C.; Zhang, N.; Scott, G.; Montoro, D.; Wittkop, T.; Mooney, S.; Melov, S.; Ellerby, L.M. Genetic correction of Huntington's disease phenotypes in induced pluripotent stem cells. Cell Stem Cell 2012, 11, 253-263.
71. Jeon, I.; Lee, N.; Li, J.-Y.; Park, I.-H.; Park, K.S.; Moon, J.; Shim, S.H.; Choi, C.; Chang, D.-J.; Kwon, J.; et al. Neuronal properties, in vivo effects, and pathology of a Huntington's disease patient-derived induced pluripotent stem cells. Stem Cells 2012, 30, 2054-2062.
72. Fink, K.D.; Rossignol, J.; Lu, M.; Leveque, X.; Hulse, T.D.; Crane, A.T.; Nerriere-Daguin, V.; Wyse, R.D.; Starski, P.A.; Schloop, M.T.; et al. Survival and Differentiation of Adenovirus-Generated Induced Pluripotent Stem Cells Transplanted into the Rat Striatum. Cell Transplant 2013, doi:10.3727/096368913X670958.
73. Fink, K.D.; Crane, A.T.; Lévèque, X.; Dues, D.J.; Huffman, L.D.; Moore, A.C.; Story, D.T.; DeJonge, R.E.; Antcliff, A.; Starski, P.A.; et al. Intrastriatal Transplantation of Adenovirus-Generated Induced Pluripotent Stem Cells for Treating Neuropathological and Functional Deficits in a Rodent Model of Huntington's Disease. Stem Cells Transl. Med. 2014, doi:10.5966/sctm.2013-0151.
74. Rossignol, J.; Fink, K.; Davis, K.; Clerc, S.; Crane, A.; Matchynski, J.; Lowrance, S.; Bombard, M.; Dekorver, N.; Lescaudron, L.; et al. Transplants of adult mesenchymal and neural stem cells provide neuroprotection and behavioral sparing in a transgenic rat model of Huntington's disease. Stem Cells 2014, 32, 500-509.
75. Aubry, L.; Bugi, A.; Lefort, N.; Rousseau, F.; Peschanski, M.; Perrier, A.L. Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proc. Natl. Acad. Sci. USA 2008, 105, 16707-16712.
76. El-Akabawy, G.; Medina, L.M.; Jeffries, A.; Price, J.; Modo, M. Purmorphamine increases DARPP-32 differentiation in human striatal neural stem cells through the Hedgehog pathway. Stem Cells Dev. 2011, 20, 1873-1887.
77. Liu, Y.; Liu, H.; Sauvey, C.; Yao, L.; Zarnowska, E.D.; Zhang, S.-C. Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat. Protoc. 2013, 8, 1670-1679