{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:03:36Z","timestamp":1792785816708,"version":"4.5.0"},"reference-count":96,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brain Repair And Intracranial Neurotherapeutics (BRAIN) Unit"},{"name":"Centre for Trials Research"},{"name":"European Union\u2019s Seventh Framework Programme","award":["602245"],"award-info":[{"award-number":["602245"]}]},{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"crossref","award":["PC1-08117"],"award-info":[{"award-number":["PC1-08117"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"crossref","award":["CLIN1-10953"],"award-info":[{"award-number":["CLIN1-10953"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005984","name":"Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021720","name":"Olav Thon Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100021720","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Lyrik Therapeutics and Sana Biotechnology","award":["EDU1-10779"],"award-info":[{"award-number":["EDU1-10779"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>There has been substantial progress in the development of regenerative medicine strategies for CNS disorders over the last decade, with progression to early clinical studies for some conditions. However, there are multiple challenges along the translational pipeline, many of which are common across diseases and pertinent to multiple donor cell types. These include defining the point at which the preclinical data are sufficiently compelling to permit progression to the first clinical studies; scaling-up, characterization, quality control and validation of the cell product; design, validation and approval of the surgical device; and operative procedures for safe and effective delivery of cell product to the brain. Furthermore, clinical trials that incorporate principles of efficient design and disease-specific outcomes are urgently needed (particularly for those undertaken in rare diseases, where relatively small cohorts are an additional limiting factor), and all processes must be adaptable in a dynamic regulatory environment.<\/jats:p>\n                  <jats:p>Here we set out the challenges associated with the clinical translation of cell therapy, using Huntington\u2019s disease as a specific example, and suggest potential strategies to address these challenges. Huntington\u2019s disease presents a clear unmet need, but, importantly, it is an autosomal dominant condition with a readily available gene test, full genetic penetrance and a wide range of associated animal models, which together mean that it is a powerful condition in which to develop principles and test experimental therapeutics. We propose that solving these challenges in Huntington\u2019s disease would provide a road map for many other neurological conditions. This white paper represents a consensus opinion emerging from a series of meetings of the international translational platforms Stem Cells for Huntington\u2019s Disease and the European Huntington\u2019s Disease Network Advanced Therapies Working Group, established to identify the challenges of cell therapy, share experience, develop guidance and highlight future directions, with the aim to expedite progress towards therapies for clinical benefit in Huntington\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awac086","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T15:12:40Z","timestamp":1646665960000},"page":"1584-1597","source":"Crossref","is-referenced-by-count":27,"title":["Translating cell therapies for neurodegenerative diseases: Huntington\u2019s disease as a model disorder"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4716-4753","authenticated-orcid":false,"given":"Anne E.","family":"Rosser","sequence":"first","affiliation":[{"name":"Cardiff University Neuroscience and Mental Health Research Institute , Hadyn Ellis Building, Cardiff CF24 4HQ, UK"},{"name":"Cardiff University Brain Repair Group, School of Biosciences , Life Sciences Building, Cardiff CF10 3AX, UK"},{"name":"Brain Repair and Intracranial Neurotherapeutics (B.R.A.I.N.) Biomedical Research Unit, College of Biomedical and Life Sciences, Cardiff University , Cardiff CF14 4EP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica E.","family":"Busse","sequence":"additional","affiliation":[{"name":"Cardiff University Centre for Trials Research, College of Biomedical and Life Sciences Cardiff University , 4th Floor Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7595-8887","authenticated-orcid":false,"given":"William P.","family":"Gray","sequence":"additional","affiliation":[{"name":"Cardiff University Neuroscience and Mental Health Research Institute , Hadyn Ellis Building, Cardiff CF24 4HQ, UK"},{"name":"Brain Repair and Intracranial Neurotherapeutics (B.R.A.I.N.) Biomedical Research Unit, College of Biomedical and Life Sciences, Cardiff University , Cardiff CF14 4EP, UK"},{"name":"University Hospital of Wales Healthcare NHS Trust, Department of Neurosurgery , Cardiff CF14 4XW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina Aron","family":"Badin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CEA, CNRS, Laboratoire des Maladies Neurod\u00e9g\u00e9n\u00e9ratives: m\u00e9canismes, th\u00e9rapies, imagerie , 92265 Fontenay-aux-Roses, France"},{"name":"Universit\u00e9 Paris-Saclay, CEA, Molecular Imaging Research Center , 92265 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anselme L.","family":"Perrier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CEA, CNRS, Laboratoire des Maladies Neurod\u00e9g\u00e9n\u00e9ratives: m\u00e9canismes, th\u00e9rapies, imagerie , 92265 Fontenay-aux-Roses, France"},{"name":"Universit\u00e9 Paris-Saclay, CEA, Molecular Imaging Research Center , 92265 Fontenay-aux-Roses, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki","family":"Wheelock","sequence":"additional","affiliation":[{"name":"University of California Davis, Department of Neurology , 95817 Sacramento, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Cozzi","sequence":"additional","affiliation":[{"name":"Transplant Immunology Unit, Department of Cardiac, Thoracic and Vascular Sciences, Padua University Hospital\u2014Ospedale Giustinianeo , Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unai Perpi\u00f1a","family":"Martin","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, and Creatio-Production and Validation Center of Advanced Therapies, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona , Barcelona, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS) , Barcelona, Spain"},{"name":"Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED) , Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Salado-Manzano","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, and Creatio-Production and Validation Center of Advanced Therapies, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona , Barcelona, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS) , Barcelona, Spain"},{"name":"Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED) , Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Mills","sequence":"additional","affiliation":[{"name":"Cardiff University Centre for Trials Research, College of Biomedical and Life Sciences Cardiff University , 4th Floor Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-6252","authenticated-orcid":false,"given":"Cheney","family":"Drew","sequence":"additional","affiliation":[{"name":"Cardiff University Centre for Trials Research, College of Biomedical and Life Sciences Cardiff University , 4th Floor Neuadd Meirionnydd, Heath Park, Cardiff CF14 4YS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Goldman","sequence":"additional","affiliation":[{"name":"Centre for Translational Neuromedicine, University of Rochester , 14642 Rochester, NY, USA"},{"name":"University of Copenhagen Faculty of Health and Medical Sciences , DK-2200 Kobenhavn, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Canals","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells and Regenerative Medicine, Department of Biomedical Sciences, and Creatio-Production and Validation Center of Advanced Therapies, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona , Barcelona, Spain"},{"name":"August Pi i Sunyer Biomedical Research Institute (IDIBAPS) , Barcelona, Spain"},{"name":"Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED) , Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"University of California Irvine, Department of Psychiatry and Human Behaviour, Department of Neurobiology and Behavior and the Sue and Bill Gross Stem Cell Center , 92697 Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"issue":"1","key":"2022060319043381700_awac086-B1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/ene.13413","article-title":"Huntington\u2019s disease: a clinical review","volume":"25","author":"McColgan","year":"2018","journal-title":"Eur J Neurol"},{"issue":"1","key":"2022060319043381700_awac086-B2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1602\/neurorx.1.1.128","article-title":"The paradigm of Huntington\u2019s disease: therapeutic opportunities in neurodegeneration","volume":"1","author":"Leegwater-Kim","year":"2004","journal-title":"NeuroRx"},{"key":"2022060319043381700_awac086-B3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-1-4939-7825-0_6","article-title":"Mouse models of Huntington\u2019s disease","volume":"1780","author":"Farshim","year":"2018","journal-title":"Methods Mol Biol"},{"issue":"1","key":"2022060319043381700_awac086-B4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S1474-4422(11)70263-0","article-title":"Potential endpoints for clinical trials in premanifest and early Huntington\u2019s disease in the TRACK-HD study: Analysis of 24 month observational data","volume":"11","author":"Tabrizi","year":"2012","journal-title":"Lancet Neurol"},{"issue":"15","key":"2022060319043381700_awac086-B5","doi-asserted-by":"crossref","first-page":"5733","DOI":"10.1073\/pnas.85.15.5733","article-title":"Differential loss of striatal projection neurons in Huntington disease","volume":"85","author":"Reiner","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022060319043381700_awac086-B6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.nbd.2013.05.004","article-title":"Challenges for taking primary and stem cells into clinical neurotransplantation trials for neurodegenerative disease","volume":"61","author":"Dunnett","year":"2014","journal-title":"Neurobiol Dis"},{"key":"2022060319043381700_awac086-B7","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/B978-0-444-59575-1.00016-8","article-title":"Clinical trials of neural transplantation in Huntington\u2019s disease","volume":"200","author":"Rosser","year":"2012","journal-title":"Prog Brain Res"},{"issue":"2","key":"2022060319043381700_awac086-B8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/stem.3300","article-title":"Cell therapy in Huntington\u2019s Disease: taking stock of past studies to move the filed forward","volume":"39","author":"Bachoud-L\u00e9vi","year":"2020","journal-title":"Stem Cells"},{"issue":"8","key":"2022060319043381700_awac086-B9","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/mds.28201","article-title":"Human fetal cell therapy in Huntington\u2019s disease: A randomized, multicenter, phase II trial","volume":"35","author":"Bachoud-L\u00e9vi","year":"2020","journal-title":"Mov Disord"},{"issue":"5","key":"2022060319043381700_awac086-B10","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.stemcr.2020.03.018","article-title":"Stem cell-derived human striatal progenitors innervate striatal targets and alleviate sensorimotor deficit in a rat model of Huntington disease","volume":"14","author":"Besusso","year":"2020","journal-title":"Stem Cell Rep"},{"issue":"1","key":"2022060319043381700_awac086-B11","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.stemcr.2017.11.005","article-title":"Human neural stem cell transplantation rescues functional deficits in R6\/2 and Q140 Huntington\u2019s disease mice","volume":"10","author":"Reidling","year":"2018","journal-title":"Stem Cell Rep"},{"issue":"7","key":"2022060319043381700_awac086-B12","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.tins.2017.05.002","article-title":"Unravelling and exploiting astrocyte dysfunction in Huntington\u2019s disease","volume":"40","author":"Khakh","year":"2017","journal-title":"Trends Neurosci"},{"key":"2022060319043381700_awac086-B13","doi-asserted-by":"crossref","first-page":"11758","DOI":"10.1038\/ncomms11758","article-title":"Human glia can both induce and rescue aspects of disease phenotype in Huntington disease","volume":"7","author":"Benraiss","year":"2016","journal-title":"Nat Commun"},{"issue":"1","key":"2022060319043381700_awac086-B14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.stem.2018.11.010","article-title":"Human ESC-derived chimeric mouse models of Huntington\u2019s disease reveal cell-intrinsic defects in glial progenitor cell differentiation","volume":"24","author":"Osipovitch","year":"2019","journal-title":"Cell Stem Cell"},{"key":"2022060319043381700_awac086-B15","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41582-020-0389-4","article-title":"Huntington disease: New insights into molecular pathogenesis and therapeutic opportunities","volume":"16","author":"Tabrizi","year":"2020","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"2022060319043381700_awac086-B16","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neuroscience.2009.01.045","article-title":"Magnetic resonance imaging of Huntington\u2019s disease: Preparing for clinical trials","volume":"164","author":"Kl\u00f6ppel","year":"2009","journal-title":"Neuroscience"},{"issue":"2","key":"2022060319043381700_awac086-B17","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3233\/JHD-210473","article-title":"Stem Cells for Huntington\u2019s disease (SC4HD): An international consortium to facilitate stem cell-based therapy for Huntington\u2019s disease","volume":"10","author":"SC4HD Consortium","year":"2021","journal-title":"J Huntingtons Dis"},{"key":"2022060319043381700_awac086-B18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-3-319-71779-1_2","article-title":"Genetic rodent models of Huntington disease","volume":"1049","author":"Stricker-Shaver","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"2022060319043381700_awac086-B19","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/B978-008045046-9.00502-7","volume-title":"Encyclopedia of Neuroscience.","author":"Alberch","year":"2009:"},{"key":"2022060319043381700_awac086-B20","first-page":"179","volume-title":"Methods in Molecular Biology","author":"Kosior","year":"; 2018"},{"key":"2022060319043381700_awac086-B21","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3389\/fncel.2020.00250","article-title":"Is the immunological response a bottleneck for cell therapy in neurodegenerative diseases?","volume":"14","author":"Salado-Manzano","year":"2020","journal-title":"Front Cell Neurosci"},{"issue":"43","key":"2022060319043381700_awac086-B22","doi-asserted-by":"crossref","first-page":"16707","DOI":"10.1073\/pnas.0808488105","article-title":"Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats","volume":"105","author":"Aubry","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"2","key":"2022060319043381700_awac086-B23","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1242\/dev.084608","article-title":"Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons","volume":"140","author":"Carri A","year":"2013","journal-title":"Development"},{"key":"2022060319043381700_awac086-B24"},{"key":"2022060319043381700_awac086-B25","year":"2007"},{"key":"2022060319043381700_awac086-B26"},{"key":"2022060319043381700_awac086-B27"},{"issue":"6","key":"2022060319043381700_awac086-B28","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1007\/s12035-020-01907-4","article-title":"Human pluripotent stem cell-derived neurons are functionally mature in vitro and integrate into the mouse striatum following transplantation","volume":"57","author":"Comella-Bolla","year":"2020","journal-title":"Mol Neurobiol"},{"issue":"1","key":"2022060319043381700_awac086-B29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.stem.2016.09.004","article-title":"Predictive markers guide differentiation to improve graft outcome in clinical translation of hESC-based therapy for Parkinson\u2019s disease","volume":"20","author":"Kirkeby","year":"2017","journal-title":"Cell Stem Cell"},{"key":"2022060319043381700_awac086-B30","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/978-1-4939-7825-0_14","article-title":"Nonhuman primate models of Huntington\u2019s disease and their application in translational research","volume":"1780","author":"Badin","year":"2018","journal-title":"Methods Mol Biol"},{"key":"2022060319043381700_awac086-B31","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/978-1-4939-7825-0_13","article-title":"Minipigs as a large-brained animal model for Huntington\u2019s disease: From behavior and imaging to gene therapy","volume":"1780","author":"Reilmann","year":"2018","journal-title":"Methods Mol Biol"},{"issue":"1","key":"2022060319043381700_awac086-B32","doi-asserted-by":"crossref","first-page":"4357","DOI":"10.1038\/s41467-019-12324-0","article-title":"MHC matching fails to prevent long-term rejection of iPSC-derived neurons in non-human primates","volume":"10","author":"Badin R","year":"2019","journal-title":"Nat Commun"},{"issue":"9","key":"2022060319043381700_awac086-B33","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1001\/jamaneurol.2019.1534","article-title":"Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: A systematic review and meta-analysis","volume":"76","author":"Bridel","year":"2019","journal-title":"JAMA Neurol"},{"issue":"458","key":"2022060319043381700_awac086-B34","doi-asserted-by":"crossref","first-page":"eaat7108","DOI":"10.1126\/scitranslmed.aat7108","article-title":"Evaluation of mutant huntingtin and neurofilament proteins as potential markers in Huntington\u2019s disease","volume":"10","author":"Byrne","year":"2018","journal-title":"Sci Transl Med"},{"issue":"2","key":"2022060319043381700_awac086-B35","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3727\/096368912X661328","article-title":"Survival of neural progenitors allografted into the CNS of immunocompetent recipients is highly dependent on transplantation site","volume":"23","author":"Janowski","year":"2014","journal-title":"Cell Transplant"},{"issue":"1","key":"2022060319043381700_awac086-B36","first-page":"S22","article-title":"Devices for cell transplantation into the central nervous system: Design considerations and emerging technologies","volume":"4","author":"Potts","year":"2013","journal-title":"Surg Neurol Int"},{"issue":"5","key":"2022060319043381700_awac086-B37","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/35072572","article-title":"Cell therapy in Parkinson\u2019s disease\u2014stop or go?","volume":"2","author":"Dunnett","year":"2001","journal-title":"Nat Rev Neurosci"},{"issue":"4","key":"2022060319043381700_awac086-B38","doi-asserted-by":"crossref","first-page":"737","DOI":"10.3727\/096368914X685429","article-title":"Translation of cell therapies to the clinic: Characteristics of cell suspensions in large-diameter injection cannulae","volume":"24","author":"Torres","year":"2015","journal-title":"Cell Transplant"},{"issue":"2","key":"2022060319043381700_awac086-B39","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1177\/096368970000900205","article-title":"Improving the survival of grafted dopaminergic neurons: A review over current approaches","volume":"9","author":"Brundin","year":"2000","journal-title":"Cell Transplant"},{"issue":"1","key":"2022060319043381700_awac086-B40","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1006\/exnr.1996.0141","article-title":"The time course of loss of dopaminergic neurons and the gliotic reaction surrounding grafts of embryonic mesencephalon to the striatum","volume":"141","author":"Barker","year":"1996","journal-title":"Exp Neurol"},{"issue":"1","key":"2022060319043381700_awac086-B41","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1186\/1750-1326-4-47","article-title":"Does neuroinflammation fan the flame in neurodegenerative diseases?","volume":"4","author":"Frank-Cannon","year":"2009","journal-title":"Mol Neurodegener"},{"issue":"11","key":"2022060319043381700_awac086-B42","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1021\/acschemneuro.8b00072","article-title":"Neuroinflammation in Huntington\u2019s disease: New insights with 11C-PBR28 PET\/MRI","volume":"9","author":"Lois","year":"2018","journal-title":"ACS Chem Neurosci"},{"issue":"6","key":"2022060319043381700_awac086-B43","doi-asserted-by":"crossref","first-page":"e890","DOI":"10.1212\/WNL.0000000000011121","article-title":"Association of dilated perivascular spaces and disease severity in patients with Huntington disease","volume":"96","author":"Chan","year":"2021","journal-title":"Neurology"},{"issue":"5","key":"2022060319043381700_awac086-B44","doi-asserted-by":"crossref","first-page":"923","DOI":"10.3171\/jns.2005.103.5.0923","article-title":"Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents","volume":"103","author":"Krauze","year":"2005","journal-title":"J Neurosurg"},{"key":"2022060319043381700_awac086-B45","doi-asserted-by":"crossref","first-page":"877","DOI":"10.5966\/sctm.2016-0269","article-title":"Magnetic resonance imaging-guided delivery of neural stem cells into the basal ganglia of nonhuman primates reveals a pulsatile mode of cell dispersion","volume":"6","author":"Malloy","year":"2017","journal-title":"Stem Cells Transl Med"},{"issue":"11\u201312","key":"2022060319043381700_awac086-B46","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.3727\/096368911X566190","article-title":"Injection parameters affect cell viability and implant volumes in automated cell delivery for the brain","volume":"20","author":"Kondziolka","year":"2011","journal-title":"Cell Transplant"},{"issue":"1","key":"2022060319043381700_awac086-B47","doi-asserted-by":"crossref","first-page":"9194","DOI":"10.1038\/s41598-018-27568-x","article-title":"Ex vivo biomechanical characterization of syringe-needle ejections for intracerebral cell delivery","volume":"8","author":"Wahlberg","year":"2018","journal-title":"Sci Rep"},{"issue":"3","key":"2022060319043381700_awac086-B48","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3171\/jns.2000.92.3.0493","article-title":"Neural transplantation cannula and microinjector system: Experimental and clinical experience - Technical note","volume":"92","author":"Mendez","year":"2000","journal-title":"J Neurosurg"},{"issue":"5","key":"2022060319043381700_awac086-B49","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nm1752","article-title":"Dopamine neurons implanted into people with Parkinson\u2019s disease survive without pathology for 14 years","volume":"14","author":"Mendez","year":"2008","journal-title":"Nat Med"},{"issue":"1","key":"2022060319043381700_awac086-B50","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/mt.2014.155","article-title":"Interventional magnetic resonance imaging-guided cell transplantation into the brain with radially branched deployment","volume":"23","author":"Silvestrini","year":"2015","journal-title":"Mol Ther"},{"issue":"1","key":"2022060319043381700_awac086-B51","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jneumeth.2007.11.032","article-title":"Survival and functional recovery of transplanted human dopaminergic neurons into hemiparkinsonian rats depend on the cannula size of the implantation instrument","volume":"169","author":"Steiner","year":"2008","journal-title":"J Neurosci Methods"},{"issue":"1","key":"2022060319043381700_awac086-B52","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1159\/000268743","article-title":"Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the G\u00f6ttingen minipig","volume":"88","author":"Bjarkam","year":"2010","journal-title":"Stereotact Funct Neurosurg"},{"issue":"7","key":"2022060319043381700_awac086-B53","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1111\/ner.12484","article-title":"Feasibility of three-dimensional placement of human therapeutic stem cells using the intracerebral microinjection instrument","volume":"19","author":"Glud","year":"2016","journal-title":"Neuromodulation"},{"issue":"1","key":"2022060319043381700_awac086-B54","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s12916-016-0722-3","article-title":"How do you design randomised trials for smaller populations? A framework","volume":"14","author":"Parmar","year":"2016","journal-title":"BMC Med"},{"key":"2022060319043381700_awac086-B55","doi-asserted-by":"crossref","first-page":"53","DOI":"10.29245\/2572-9411\/2016\/3.1054","article-title":"Design and analysis of clinical trials for small rare disease populations","volume":"1","author":"Hilfers","year":"2016","journal-title":"J Rare Dis Res Treat"},{"key":"2022060319043381700_awac086-B56","doi-asserted-by":"crossref","first-page":"g6802","DOI":"10.1136\/bmj.g6802","article-title":"Innovative research methods for studying treatments for rare diseases: methodological review","volume":"349","author":"Gagne","year":"2014","journal-title":"BMJ"},{"issue":"15","key":"2022060319043381700_awac086-B57","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1093\/eurheartj\/ehs114","article-title":"Do observational studies using propensity score methods agree with randomized trials? A systematic comparison of studies on acute coronary syndromes","volume":"33","author":"Dahabreh","year":"2012","journal-title":"Eur Heart J"},{"issue":"1","key":"2022060319043381700_awac086-B58","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/SLA.0000000000000256","article-title":"Comparison of treatment effect estimates from prospective nonrandomized studies with propensity score analysis and randomized controlled trials of surgical procedures","volume":"259","author":"Lonjon","year":"2014","journal-title":"Ann Surg"},{"issue":"2","key":"2022060319043381700_awac086-B59","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1308\/rcsbull.2016.75","article-title":"When should placebo surgery as a control in clinical trials be carried out?","volume":"98","author":"George","year":"2016","journal-title":"Bull R Coll Surg Engl"},{"key":"2022060319043381700_awac086-B60","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.parkreldis.2021.01.006","article-title":"The use of wearable\/portable digital sensors in Huntington\u2019s disease: A systematic review","volume":"83","author":"Tortelli","year":"2021","journal-title":"Park Relat Disord"},{"issue":"1","key":"2022060319043381700_awac086-B61","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2217\/fnl.10.78","article-title":"Cell transplantation for Huntington\u2019s disease: practical and clinical considerations","volume":"6","author":"Rosser","year":"2011","journal-title":"Future Neurol"},{"issue":"11","key":"2022060319043381700_awac086-B62","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/S1474-4422(18)30294-1","article-title":"Biological and clinical manifestations of juvenile Huntington\u2019s disease: a retrospective analysis","volume":"17","author":"Fusilli","year":"2018","journal-title":"Lancet Neurol"},{"issue":"1","key":"2022060319043381700_awac086-B63","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/cge.13857","article-title":"Age of onset and behavioral manifestations in Huntington\u2019s disease: An Enroll-HD cohort analysis","volume":"99","author":"Ranganathan","year":"2021","journal-title":"Clin Genet"},{"key":"2022060319043381700_awac086-B64","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fnint.2011.00078","article-title":"The current status of neural grafting in the treatment of Huntington\u2019s disease. A review","volume":"5","author":"Wijeyekoon","year":"2011","journal-title":"Front Integr Neurosci"},{"issue":"3","key":"2022060319043381700_awac086-B65","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0306-4522(96)00657-4","article-title":"The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. II. Correlation between positron emission tomography and reaching behaviour","volume":"79","author":"Fricker","year":"1997","journal-title":"Neuroscience"},{"issue":"4","key":"2022060319043381700_awac086-B66","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S1474-4422(06)70381-7","article-title":"Effect of fetal neural transplants in patients with Huntington\u2019s disease 6 years after surgery: a long-term follow-up study","volume":"5","author":"Bachoud-Levi","year":"2006","journal-title":"Lancet Neurol"},{"issue":"5","key":"2022060319043381700_awac086-B67","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1212\/WNL.58.5.687","article-title":"Bilateral human fetal striatal transplantation in Huntington\u2019s disease","volume":"58","author":"Hauser","year":"2002","journal-title":"Neurology"},{"issue":"2","key":"2022060319043381700_awac086-B68","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/mds.870110205","article-title":"Core assessment program for intracerebral transplantation in Huntington\u2019s disease (CAPIT-HD)","volume":"11","author":"Quinn","year":"1996","journal-title":"Mov Disord"},{"issue":"8","key":"2022060319043381700_awac086-B69","doi-asserted-by":"crossref","first-page":"e0253064","DOI":"10.1371\/journal.pone.0253064","article-title":"Cognitive decline in Huntington\u2019s disease in the digitalized arithmetic task (DAT)","volume":"16","author":"Lunven","year":"2021","journal-title":"PLoS One"},{"issue":"5","key":"2022060319043381700_awac086-B70","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1172\/JCI80743","article-title":"Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington\u2019s disease patients","volume":"125","author":"Wild","year":"2015","journal-title":"J Clin Invest"},{"issue":"6","key":"2022060319043381700_awac086-B71","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/0090-3019(94)90082-5","article-title":"Angiogenesis and the blood-brain barrier in intracerebral solid and cell suspension grafts","volume":"42","author":"Akalan","year":"1994","journal-title":"Surg Neurol"},{"issue":"2","key":"2022060319043381700_awac086-B72","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000502000","article-title":"Traditional and digital biomarkers: Two worlds apart?","volume":"3","author":"Babrak","year":"2019","journal-title":"Digit Biomarkers"},{"issue":"1","key":"2022060319043381700_awac086-B73","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000477383","article-title":"The first frontier: Digital biomarkers for neurodegenerative disorders","volume":"1","author":"Dorsey","year":"2017","journal-title":"Digit Biomarkers"},{"issue":"1","key":"2022060319043381700_awac086-B74","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1006\/exnr.1997.6685","article-title":"Safety of intrastriatal neurotransplantation for Huntington\u2019s disease patients","volume":"149","author":"Kopyov","year":"1998","journal-title":"Exp Neurol"},{"issue":"6","key":"2022060319043381700_awac086-B75","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1136\/jnnp.73.6.678","article-title":"Unilateral transplantation of human primary fetal tissue in four patients with Huntington\u2019s disease: NEST-UK safety report ISRCTN no 36485475","volume":"73","author":"Rosser","year":"2002","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"5","key":"2022060319043381700_awac086-B76","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3727\/096368913X676222","article-title":"Donor-specific anti-HLA antibodies in Huntington\u2019s disease recipients of human fetal striatal grafts","volume":"24","author":"Porfirio","year":"2013","journal-title":"Cell Transplant"},{"issue":"1","key":"2022060319043381700_awac086-B77","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3233\/JHD-130049","article-title":"A critical evaluation of inflammatory markers in huntingtons disease plasma","volume":"2","author":"Silajd\u017ei\u0107","year":"2013","journal-title":"J Huntingtons Dis"},{"key":"2022060319043381700_awac086-B78","doi-asserted-by":"crossref","first-page":"8653132","DOI":"10.1155\/2016\/8653132","article-title":"Neuroimmunology of Huntington\u2019s disease: Revisiting evidence from human studies","volume":"2016","author":"Rocha","year":"2016","journal-title":"Mediators Inflamm"},{"issue":"6779","key":"2022060319043381700_awac086-B79","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/35008142","article-title":"Delaying the onset of Huntington\u2019s in mice","volume":"404","author":"Van Dellen","year":"2000","journal-title":"Nature"},{"issue":"3","key":"2022060319043381700_awac086-B80","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.neuroscience.2005.01.016","article-title":"Training specificity, graft development and graft-mediated functional recovery in a rodent model of Huntington\u2019s disease","volume":"132","author":"D\u00f6br\u00f6ssy","year":"2005","journal-title":"Neuroscience"},{"issue":"1","key":"2022060319043381700_awac086-B81","doi-asserted-by":"crossref","first-page":"e166","DOI":"10.1371\/journal.pone.0000166","article-title":"Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington\u2019s disease","volume":"2","author":"Krystkowiak","year":"2007","journal-title":"PLoS One"},{"issue":"6","key":"2022060319043381700_awac086-B82","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1002\/ana.25354","article-title":"Outcome of cell suspension allografts in a patient with Huntington\u2019s disease","volume":"84","author":"Maxan","year":"2018","journal-title":"Ann Neurol"},{"issue":"1","key":"2022060319043381700_awac086-B83","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1159\/000098976","article-title":"Stereotactic technique and pathophysiological mechanisms of neurotransplantation in huntington\u2019s chorea","volume":"58","author":"\u0160ramka","year":"1992","journal-title":"Stereotact Funct Neurosurg"},{"issue":"30","key":"2022060319043381700_awac086-B84","doi-asserted-by":"crossref","first-page":"12483","DOI":"10.1073\/pnas.0904239106","article-title":"Neural transplants in patients with Huntington\u2019s disease undergo disease-like neuronal degeneration","volume":"106","author":"Cicchetti","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"2022060319043381700_awac086-B85","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1080\/01616412.1995.11740334","article-title":"Fetal striatal homotransplantation for Huntington\u2019s disease: First two case reports","volume":"17","author":"Madrazo","year":"1995","journal-title":"Neurol Res"},{"issue":"8","key":"2022060319043381700_awac086-B86","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1136\/jnnp.2007.142380","article-title":"Long-term clinical and positron emission tomography outcome of fetal striatal transplantation in Huntington\u2019s disease","volume":"79","author":"Reuter","year":"2008","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"9246","key":"2022060319043381700_awac086-B87","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/S0140-6736(00)03310-9","article-title":"Motor and cognitive improvements in patients with Huntington\u2019s disease after neural transplantation","volume":"356","author":"Bachoud-L\u00e9vi","year":"2000","journal-title":"Lancet"},{"issue":"4","key":"2022060319043381700_awac086-B88","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.stemcr.2013.08.007","article-title":"Direct comparison of autologous and allogeneic transplantation of IPSC-derived neural cells in the brain of a nonhuman primate","volume":"1","author":"Morizane","year":"2013","journal-title":"Stem Cell Rep"},{"issue":"7350","key":"2022060319043381700_awac086-B89","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nature10135","article-title":"Immunogenicity of induced pluripotent stem cells","volume":"474","author":"Zhao","year":"2011","journal-title":"Nature"},{"issue":"3","key":"2022060319043381700_awac086-B90","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.stem.2015.07.021","article-title":"Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells","volume":"17","author":"Zhao","year":"2015","journal-title":"Cell Stem Cell"},{"issue":"3","key":"2022060319043381700_awac086-B91","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2217\/rme.15.1","article-title":"Development of a global network of induced pluripotent stem cell haplobanks","volume":"10","author":"Wilmut","year":"2015","journal-title":"Regen Med"},{"issue":"11","key":"2022060319043381700_awac086-B92","doi-asserted-by":"crossref","first-page":"983","DOI":"10.2217\/rme-2019-0117","article-title":"Engineering strategies for generating hypoimmunogenic cells with high clinical and commercial value","volume":"14","author":"Malik","year":"2019","journal-title":"Regen Med"},{"issue":"4","key":"2022060319043381700_awac086-B93","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.stem.2019.02.005","article-title":"Targeted disruption of HLA genes via CRISPR-Cas9 generates iPSCs with enhanced immune compatibility","volume":"24","author":"Xu","year":"2019","journal-title":"Cell Stem Cell"},{"issue":"1","key":"2022060319043381700_awac086-B94","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s41467-017-00926-5","article-title":"MHC matching improves engraftment of iPSC-derived neurons in non-human primates","volume":"8","author":"Morizane","year":"2017","journal-title":"Nat Commun"},{"issue":"1","key":"2022060319043381700_awac086-B95","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.stem.2013.11.014","article-title":"An effective approach to prevent immune rejection of human ESC-derived allografts","volume":"14","author":"Rong","year":"2014","journal-title":"Cell Stem Cell"},{"issue":"8","key":"2022060319043381700_awac086-B96","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/nbt.3860","article-title":"HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells","volume":"35","author":"Gornalusse","year":"2017","journal-title":"Nat Biotechnol"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awac086\/43691368\/awac086.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/145\/5\/1584\/43948428\/awac086.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/145\/5\/1584\/43948428\/awac086.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T17:58:51Z","timestamp":1726768731000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/145\/5\/1584\/6545253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,9]]},"references-count":96,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3,9]]},"published-print":{"date-parts":[[2022,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awac086","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5,1]]},"published":{"date-parts":[[2022,3,9]]}}}