{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:26:21Z","timestamp":1791923181417,"version":"4.3.4"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Regen Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Huntington\u2019s disease (HD) is a dominantly inherited monogenetic disorder characterized by motor and cognitive dysfunction due to neurodegeneration. The disease is caused by the polyglutamine (polyQ) expansion at the 5\u2032 terminal of the exon 1 of the huntingtin (<jats:italic>HTT<\/jats:italic>) gene, <jats:italic>IT15<\/jats:italic>, which results in the accumulation of mutant HTT (mHTT) aggregates in neurons and cell death. The monogenetic cause and the loss of specific neural cell population make HD a suitable candidate for stem cell and gene therapy. In this study, we demonstrate the efficacy of the combination of stem cell and gene therapy in a transgenic HD mouse model (N171-82Q; HD mice) using rhesus monkey (<jats:italic>Macaca mulatta<\/jats:italic>) neural progenitor cells (NPCs). We have established monkey NPC cell lines from induced pluripotent stem cells (iPSCs) that can differentiate into GABAergic neurons in vitro as well as in mouse brains without tumor formation. Wild-type monkey NPCs (WT-NPCs), NPCs derived from a transgenic HD monkey (HD-NPCs), and genetically modified HD-NPCs with reduced mHTT levels by stable expression of small-hairpin RNA (HD-shHD-NPCs), were grafted into the striatum of WT and HD mice. Mice that received HD-shHD-NPC grafts showed a significant increase in lifespan compared to the sham injection group and HD mice. Both WT-NPC and HD-shHD-NPC grafts in HD mice showed significant improvement in motor functions assessed by rotarod and grip strength. Also, immunohistochemistry demonstrated the integration and differentiation. Our results suggest the combination of stem cell and gene therapy as a viable therapeutic option for HD treatment.<\/jats:p>","DOI":"10.1038\/s41536-019-0066-7","type":"journal-article","created":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T11:03:26Z","timestamp":1553598206000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Combination of stem cell and gene therapy ameliorates symptoms in Huntington\u2019s disease mice"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-9128","authenticated-orcid":false,"given":"In Ki","family":"Cho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carissa Emerson","family":"Hunter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvince Learnz","family":"Pongos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony Wing Sang","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,26]]},"reference":[{"key":"66_CR1","doi-asserted-by":"crossref","unstructured":"Bates, G. P. et al. Huntington disease. Nat. Rev. Dis. Primers 1, 15005 (2015).","DOI":"10.1038\/nrdp.2015.5"},{"key":"66_CR2","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/BF00401235","volume":"73","author":"JG van Dijk","year":"1986","unstructured":"van Dijk, J. G., van der Velde, E. A., Roos, R. A. & Bruyn, G. W. Juvenile Huntington disease. Hum. Genet. 73, 235\u2013239 (1986).","journal-title":"Hum. Genet."},{"key":"66_CR3","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-40","volume":"5","author":"RA Roos","year":"2010","unstructured":"Roos, R. A. Huntington\u2019s disease: a clinical review. Orphanet J. Rare Dis. 5, 40 (2010).","journal-title":"Orphanet J. Rare Dis."},{"key":"66_CR4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fnagi.2013.00012","volume":"5","author":"KM Biglan","year":"2013","unstructured":"Biglan, K. M. et al. Refining the diagnosis of Huntington disease: the PREDICT-HD study. Front. Aging Neurosci. 5, 12 (2013).","journal-title":"Front. Aging Neurosci."},{"key":"66_CR5","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1212\/01.wnl.0000238390.86304.4e","volume":"67","author":"G Yoon","year":"2006","unstructured":"Yoon, G. et al. Speech and language delay are early manifestations of juvenile-onset Huntington disease. Neurology 67, 1265\u20131267 (2006).","journal-title":"Neurology"},{"key":"66_CR6","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1136\/jmg.30.12.982","volume":"30","author":"ME MacDonald","year":"1993","unstructured":"MacDonald, M. E. et al. Gametic but not somatic instability of CAG repeat length in Huntington\u2019s disease. J. Med. Genet. 30, 982\u2013986 (1993).","journal-title":"J. Med. Genet."},{"key":"66_CR7","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/ng0893-393","volume":"4","author":"RG Snell","year":"1993","unstructured":"Snell, R. G. et al. Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington\u2019s disease. Nat. Genet. 4, 393\u2013397 (1993).","journal-title":"Nat. Genet."},{"key":"66_CR8","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.1111\/j.1460-9568.2008.06310.x","volume":"27","author":"JM Gil","year":"2008","unstructured":"Gil, J. M. & Rego, A. C. Mechanisms of neurodegeneration in Huntington\u2019s disease. Eur. J. Neurosci. 27, 2803\u20132820 (2008).","journal-title":"Eur. J. Neurosci."},{"key":"66_CR9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.3233\/JHD-130072","volume":"2","author":"ZR Crook","year":"2013","unstructured":"Crook, Z. R. & Housman, D. E. Surveying the landscape of Huntington\u2019s disease mechanisms, measurements, and medicines. J. Huntingtons Dis. 2, 405\u2013436 (2013).","journal-title":"J. Huntingtons Dis."},{"key":"66_CR10","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1006\/exnr.1998.7005","volume":"156","author":"KA Sieradzan","year":"1999","unstructured":"Sieradzan, K. A. et al. Huntington\u2019s disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exp. Neurol. 156, 92\u201399 (1999).","journal-title":"Exp. Neurol."},{"key":"66_CR11","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","volume":"277","author":"M DiFiglia","year":"1997","unstructured":"DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990\u20131993 (1997).","journal-title":"Science"},{"key":"66_CR12","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1038\/mt.2012.191","volume":"20","author":"BL Davidson","year":"2012","unstructured":"Davidson, B. L. Taking a break from huntingtin. Mol. Ther. 20, 1838 (2012).","journal-title":"Mol. Ther."},{"key":"66_CR13","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.cell.2012.08.008","volume":"150","author":"BL Davidson","year":"2012","unstructured":"Davidson, B. L. & Monteys, A. M. Singles engage the RNA interference pathway. Cell 150, 873\u2013875 (2012).","journal-title":"Cell"},{"key":"66_CR14","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.cell.2012.08.014","volume":"150","author":"WF Lima","year":"2012","unstructured":"Lima, W. F. et al. Single-stranded siRNAs activate RNAi in animals. Cell 150, 883\u2013894 (2012).","journal-title":"Cell"},{"key":"66_CR15","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.cell.2012.08.002","volume":"150","author":"D Yu","year":"2012","unstructured":"Yu, D. et al. Single-stranded RNAs use RNAi to potently and allele-selectively inhibit mutant huntingtin expression. Cell 150, 895\u2013908 (2012).","journal-title":"Cell"},{"key":"66_CR16","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1038\/mt.2011.201","volume":"19","author":"JB Carroll","year":"2011","unstructured":"Carroll, J. B. et al. Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene\/allele-specific silencing of mutant huntingtin. Mol. Ther. 19, 2178\u20132185 (2011).","journal-title":"Mol. Ther."},{"key":"66_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099341","volume":"9","author":"V Drouet","year":"2014","unstructured":"Drouet, V. et al. Allele-specific silencing of mutant huntingtin in rodent brain and human stem cells. PLoS One 9, e99341 (2014).","journal-title":"PLoS One"},{"key":"66_CR18","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.ymthe.2016.11.010","volume":"25","author":"AM Monteys","year":"2017","unstructured":"Monteys, A. M., Ebanks, S. A., Keiser, M. S. & Davidson, B. L. CRISPR\/Cas9 editing of the mutant huntingtin allele in vitro and in vivo. Mol. Ther. 25, 12\u201323 (2017).","journal-title":"Mol. Ther."},{"key":"66_CR19","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1172\/JCI92087","volume":"127","author":"S Yang","year":"2017","unstructured":"Yang, S. et al. CRISPR\/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington\u2019s disease. J. Clin. Invest. 127, 2719\u20132724 (2017).","journal-title":"J. Clin. Invest."},{"key":"66_CR20","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1038\/mt.2009.17","volume":"17","author":"RL Boudreau","year":"2009","unstructured":"Boudreau, R. L. et al. Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington\u2019s disease mice. Mol. Ther. 17, 1053\u20131063 (2009).","journal-title":"Mol. Ther."},{"key":"66_CR21","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1038\/mt.2011.219","volume":"19","author":"JL McBride","year":"2011","unstructured":"McBride, J. L. et al. Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington\u2019s disease. Mol. Ther. 19, 2152\u20132162 (2011).","journal-title":"Mol. Ther."},{"key":"66_CR22","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.stemcr.2014.07.011","volume":"3","author":"RL Carter","year":"2014","unstructured":"Carter, R. L. et al. Reversal of cellular phenotypes in neural cells derived from Huntington\u2019s disease monkey-induced pluripotent stem cells. Stem Cell Rep. 3, 585\u2013593 (2014).","journal-title":"Stem Cell Rep."},{"key":"66_CR23","doi-asserted-by":"publisher","first-page":"3359","DOI":"10.1073\/pnas.1524575113","volume":"113","author":"G Wang","year":"2016","unstructured":"Wang, G., Liu, X., Gaertig, M. A., Li, S. & Li, X. J. Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis. Proc. Natl. Acad. Sci. U.S.A. 113, 3359\u20133364 (2016).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"66_CR24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006846","volume":"13","author":"P Dietrich","year":"2017","unstructured":"Dietrich, P., Johnson, I. M., Alli, S. & Dragatsis, I. Elimination of huntingtin in the adult mouse leads to progressive behavioral deficits, bilateral thalamic calcification, and altered brain iron homeostasis. PLoS Genet. 13, e1006846 (2017).","journal-title":"PLoS Genet."},{"key":"66_CR25","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/S1474-4422(17)30280-6","volume":"16","author":"EJ Wild","year":"2017","unstructured":"Wild, E. J. & Tabrizi, S. J. Therapies targeting DNA and RNA in Huntington\u2019s disease. Lancet Neurol. 16, 837\u2013847 (2017).","journal-title":"Lancet Neurol."},{"key":"66_CR26","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/nature06975","volume":"453","author":"SH Yang","year":"2008","unstructured":"Yang, S. H. et al. Towards a transgenic model of Huntington\u2019s disease in a non-human primate. Nature 453, 921\u2013924 (2008).","journal-title":"Nature"},{"key":"66_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00381-8","volume":"7","author":"Y Meng","year":"2017","unstructured":"Meng, Y., Jiang, J., Bachevalier, J., Zhang, X. & Chan, A. W. Developmental whole brain white matter alterations in transgenic Huntington\u2019s disease monkey. Sci. Rep. 7, 379 (2017).","journal-title":"Sci. Rep."},{"key":"66_CR28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122335","volume":"10","author":"AW Chan","year":"2015","unstructured":"Chan, A. W. et al. Progressive cognitive deficit, motor impairment and striatal pathology in a transgenic Huntington disease monkey model from infancy to adulthood. PLoS One 10, e0122335 (2015).","journal-title":"PLoS One"},{"key":"66_CR29","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1089\/cell.2010.0019","volume":"12","author":"AW Chan","year":"2010","unstructured":"Chan, A. W., Cheng, P. H., Neumann, A. & Yang, J. J. Reprogramming Huntington monkey skin cells into pluripotent stem cells. Cell Reprogram. 12, 509\u2013517 (2010).","journal-title":"Cell Reprogram."},{"key":"66_CR30","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1177\/2472555216685044","volume":"22","author":"T Kunkanjanawan","year":"2017","unstructured":"Kunkanjanawan, T. et al. Induced pluripotent HD monkey stem cells derived neural cells for drug discovery. SLAS Discov. 22, 696\u2013705 (2017).","journal-title":"SLAS Discov."},{"key":"66_CR31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162788","volume":"11","author":"T Kunkanjanawan","year":"2016","unstructured":"Kunkanjanawan, T. et al. miR-196a ameliorates cytotoxicity and cellular phenotype in transgenic Huntington\u2019s disease monkey neural cells. PLoS One 11, e0162788 (2016).","journal-title":"PLoS One"},{"key":"66_CR32","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nrneurol.2014.24","volume":"10","author":"CA Ross","year":"2014","unstructured":"Ross, C. A. et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat. Rev. Neurol. 10, 204\u2013216 (2014).","journal-title":"Nat. Rev. Neurol."},{"key":"66_CR33","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1136\/mp.54.6.409","volume":"54","author":"S Davies","year":"2001","unstructured":"Davies, S. & Ramsden, D. B. Huntington\u2019s disease. Mol. Pathol. 54, 409\u2013413 (2001).","journal-title":"Mol. Pathol."},{"key":"66_CR34","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1750-1326-1-19","volume":"1","author":"S Li","year":"2006","unstructured":"Li, S. & Li, X. J. Multiple pathways contribute to the pathogenesis of Huntington disease. Mol. Neurodegener. 1, 19 (2006).","journal-title":"Mol. Neurodegener."},{"key":"66_CR35","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1097\/00005072-199805000-00001","volume":"57","author":"JP Vonsattel","year":"1998","unstructured":"Vonsattel, J. P. & DiFiglia, M. Huntington disease. J. Neuropathol. Exp. Neurol. 57, 369\u2013384 (1998).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"66_CR36","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","volume":"126","author":"K Takahashi","year":"2006","unstructured":"Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663\u2013676 (2006).","journal-title":"Cell"},{"key":"66_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-7-46","volume":"7","author":"J Kocerha","year":"2014","unstructured":"Kocerha, J., Xu, Y., Prucha, M. S., Zhao, D. & Chan, A. W.microRNA-128a dysregulation in transgenic Huntington\u2019s disease monkeys. Mol. Brain 7, 46 (2014).","journal-title":"Mol. Brain"},{"key":"66_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-014-0060-2","volume":"7","author":"A Neueder","year":"2014","unstructured":"Neueder, A. & Bates, G. P. A common gene expression signature in Huntington\u2019s disease patient brain regions. BMC Med. Genomics 7, 60 (2014).","journal-title":"BMC Med. Genomics"},{"key":"66_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143563","volume":"10","author":"A Labadorf","year":"2015","unstructured":"Labadorf, A. et al. RNA sequence analysis of human Huntington disease brain reveals an extensive increase in inflammatory and developmental gene expression. PLoS One 10, e0143563 (2015).","journal-title":"PLoS One"},{"key":"66_CR40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107434","volume":"9","author":"NH Skotte","year":"2014","unstructured":"Skotte, N. H. et al. Allele-specific suppression of mutant huntingtin using antisense oligonucleotides: providing a therapeutic option for all Huntington disease patients. PLoS One 9, e107434 (2014).","journal-title":"PLoS One"},{"key":"66_CR41","doi-asserted-by":"publisher","first-page":"10166","DOI":"10.1021\/bi101208k","volume":"49","author":"KT Gagnon","year":"2010","unstructured":"Gagnon, K. T. et al. Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat. Biochemistry 49, 10166\u201310178 (2010).","journal-title":"Biochemistry"},{"key":"66_CR42","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1089\/hum.2013.200","volume":"25","author":"LM Stanek","year":"2014","unstructured":"Stanek, L. M. et al. Silencing mutant huntingtin by adeno-associated virus-mediated RNA interference ameliorates disease manifestations in the YAC128 mouse model of Huntington\u2019s disease. Hum. Gene Ther. 25, 461\u2013474 (2014).","journal-title":"Hum. Gene Ther."},{"key":"66_CR43","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.bbrc.2017.05.040","volume":"488","author":"JJ Ban","year":"2017","unstructured":"Ban, J. J., Chung, J. Y., Lee, M., Im, W. & Kim, M. MicroRNA-27a reduces mutant hutingtin aggregation in an in vitro model of Huntington\u2019s disease. Biochem. Biophys. Res. Commun. 488, 316\u2013321 (2017).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"66_CR44","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/gt.2017.71","volume":"24","author":"J Miniarikova","year":"2017","unstructured":"Miniarikova, J. et al. AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington\u2019s disease. Gene Ther. 24, 630\u2013639 (2017).","journal-title":"Gene Ther."},{"key":"66_CR45","doi-asserted-by":"publisher","first-page":"E3136","DOI":"10.1073\/pnas.1206506109","volume":"109","author":"M Garriga-Canut","year":"2012","unstructured":"Garriga-Canut, M. et al. Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6\/2 mice. Proc. Natl. Acad. Sci. U.S.A. 109, E3136\u2013E3145 (2012).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"66_CR46","doi-asserted-by":"publisher","first-page":"2980","DOI":"10.1016\/j.celrep.2017.08.075","volume":"20","author":"N Merienne","year":"2017","unstructured":"Merienne, N. et al. The self-inactivating KamiCas9 system for the editing of CNS disease genes. Cell Rep. 20, 2980\u20132991 (2017).","journal-title":"Cell Rep."},{"key":"66_CR47","first-page":"4566","volume":"25","author":"JW Shin","year":"2016","unstructured":"Shin, J. W. et al. Permanent inactivation of Huntington\u2019s disease mutation by personalized allele-specific CRISPR\/Cas9. Hum. Mol. Genet. 25, 4566\u20134576 (2016).","journal-title":"Hum. Mol. Genet."},{"key":"66_CR48","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1006\/mcne.2000.0872","volume":"16","author":"C Nellemann","year":"2000","unstructured":"Nellemann, C. et al. Inhibition of Huntington synthesis by antisense oligodeoxynucleotides. Mol. Cell. Neurosci. 16, 313\u2013323 (2000).","journal-title":"Mol. Cell. Neurosci."},{"key":"66_CR49","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/j.1749-6632.2009.04975.x","volume":"1175","author":"J Hu","year":"2009","unstructured":"Hu, J., Matsui, M. & Corey, D. R. Allele-selective inhibition of mutant huntingtin by peptide nucleic acid-peptide conjugates, locked nucleic acid, and small interfering RNA. Ann. N. Y. Acad. Sci. 1175, 24\u201331 (2009).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"66_CR50","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1073\/pnas.0501507102","volume":"102","author":"SQ Harper","year":"2005","unstructured":"Harper, S. Q. et al. RNA interference improves motor and neuropathological abnormalities in a Huntington\u2019s disease mouse model. Proc. Natl. Acad. Sci. U.S.A. 102, 5820\u20135825 (2005).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"66_CR51","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.lfs.2015.10.025","volume":"152","author":"S Dutta","year":"2016","unstructured":"Dutta, S. & Sengupta, P. Men and mice: relating their ages. Life Sci. 152, 244\u2013248 (2016).","journal-title":"Life Sci."},{"key":"66_CR52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009347","volume":"5","author":"BR Snyder","year":"2010","unstructured":"Snyder, B. R., Chiu, A. M., Prockop, D. J. & Chan, A. W. Human multipotent stromal cells (MSCs) increase neurogenesis and decrease atrophy of the striatum in a transgenic mouse model for Huntington\u2019s disease. PLoS One 5, e9347 (2010).","journal-title":"PLoS One"},{"key":"66_CR53","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.stem.2013.04.005","volume":"12","author":"CR Nicholas","year":"2013","unstructured":"Nicholas, C. R. et al. Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell 12, 573\u2013586 (2013).","journal-title":"Cell Stem Cell"},{"key":"66_CR54","doi-asserted-by":"publisher","first-page":"16825","DOI":"10.1073\/pnas.1108077108","volume":"108","author":"S Nori","year":"2011","unstructured":"Nori, S. et al. Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc. Natl. Acad. Sci. U.S.A. 108, 16825\u201316830 (2011).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"66_CR55","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/jnr.21817","volume":"87","author":"CR Yang","year":"2009","unstructured":"Yang, C. R. & Yu, R. K. Intracerebral transplantation of neural stem cells combined with trehalose ingestion alleviates pathology in a mouse model of Huntington\u2019s disease. J. Neurosci. Res. 87, 26\u201333 (2009).","journal-title":"J. Neurosci. Res."},{"key":"66_CR56","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.neubiorev.2017.02.017","volume":"77","author":"AM Tartaglione","year":"2017","unstructured":"Tartaglione, A. M., Popoli, P. & Calamandrei, G. Regenerative medicine in Huntington\u2019s disease: strengths and weaknesses of preclinical studies. Neurosci. Biobehav. Rev. 77, 32\u201347 (2017).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"66_CR57","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1016\/j.drudis.2014.02.012","volume":"19","author":"Y Chen","year":"2014","unstructured":"Chen, Y., Carter, R. L., Cho, I. K. & Chan, A. W. S. Cell-based therapies for Huntington\u2019s disease. Drug Discov. Today 19, 980\u2013984 (2014).","journal-title":"Drug Discov. Today"},{"key":"66_CR58","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/scrt41","volume":"1","author":"EM Vazey","year":"2010","unstructured":"Vazey, E. M. & Connor, B. Differential fate and functional outcome of lithium chloride primed adult neural progenitor cell transplants in a rat model of Huntington disease. Stem Cell Res. Ther. 1, 41 (2010).","journal-title":"Stem Cell Res. Ther."},{"key":"66_CR59","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.expneurol.2016.04.003","volume":"281","author":"GR Linares","year":"2016","unstructured":"Linares, G. R. et al. Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington\u2019s disease. Exp. Neurol. 281, 81\u201392 (2016).","journal-title":"Exp. Neurol."},{"key":"66_CR60","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1002\/stem.1508","volume":"32","author":"J Rossignol","year":"2014","unstructured":"Rossignol, J. et al. Transplants of adult mesenchymal and neural stem cells provide neuroprotection and behavioral sparing in a transgenic rat model of Huntington\u2019s disease. Stem Cells 32, 500\u2013509 (2014).","journal-title":"Stem Cells"},{"key":"66_CR61","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.bbr.2010.05.023","volume":"214","author":"ND Dey","year":"2010","unstructured":"Dey, N. D. et al. Genetically engineered mesenchymal stem cells reduce behavioral deficits in the YAC 128 mouse model of Huntington\u2019s disease. Behav. Brain Res. 214, 193\u2013200 (2010).","journal-title":"Behav. Brain Res."},{"key":"66_CR62","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.celrep.2013.02.016","volume":"3","author":"ME Emborg","year":"2013","unstructured":"Emborg, M. E. et al. Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain. Cell Rep. 3, 646\u2013650 (2013).","journal-title":"Cell Rep."},{"key":"66_CR63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049469","volume":"7","author":"H Shimada","year":"2012","unstructured":"Shimada, H. et al. Efficient derivation of multipotent neural stem\/progenitor cells from non-human primate embryonic stem cells. PLoS One 7, e49469 (2012).","journal-title":"PLoS One"},{"key":"66_CR64","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1002\/stem.1415","volume":"31","author":"M Sundberg","year":"2013","unstructured":"Sundberg, M. et al. Improved cell therapy protocols for Parkinson\u2019s disease based on differentiation efficiency and safety of hESC-, hiPSC-, and non-human primate iPSC-derived dopaminergic neurons. Stem Cells 31, 1548\u20131562 (2013).","journal-title":"Stem Cells"},{"key":"66_CR65","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.stem.2015.01.018","volume":"16","author":"PJ Hallett","year":"2015","unstructured":"Hallett, P. J. et al. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson\u2019s disease. Cell Stem Cell 16, 269\u2013274 (2015).","journal-title":"Cell Stem Cell"},{"key":"66_CR66","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.stemcr.2013.08.007","volume":"1","author":"A Morizane","year":"2013","unstructured":"Morizane, A. et al. Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate. Stem Cell Rep. 1, 283\u2013292 (2013).","journal-title":"Stem Cell Rep."},{"key":"66_CR67","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.biomaterials.2014.10.056","volume":"39","author":"W Li","year":"2015","unstructured":"Li, W. et al. Engraftable neural crest stem cells derived from cynomolgus monkey embryonic stem cells. Biomaterials 39, 75\u201384 (2015).","journal-title":"Biomaterials"},{"key":"66_CR68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041120","volume":"7","author":"MM Daadi","year":"2012","unstructured":"Daadi, M. M., Grueter, B. A., Malenka, R. C., Redmond, D. E. Jr. & Steinberg, G. K. Dopaminergic neurons from midbrain-specified human embryonic stem cell-derived neural stem cells engrafted in a monkey model of Parkinson\u2019s disease. PLoS One 7, e41120 (2012).","journal-title":"PLoS One"},{"key":"66_CR69","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-15-36","volume":"15","author":"AW Chan","year":"2014","unstructured":"Chan, A. W. et al. A two years longitudinal study of a transgenic Huntington disease monkey. BMC Neurosci. 15, 36 (2014).","journal-title":"BMC Neurosci."}],"container-title":["npj Regenerative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41536-019-0066-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41536-019-0066-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41536-019-0066-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T03:08:32Z","timestamp":1671246512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41536-019-0066-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,26]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["66"],"URL":"https:\/\/doi.org\/10.1038\/s41536-019-0066-7","relation":{},"ISSN":["2057-3995"],"issn-type":[{"value":"2057-3995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,26]]},"assertion":[{"value":"6 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7"}}