{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T10:38:19Z","timestamp":1752230299784},"reference-count":38,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Neurol"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of cellular transplantation to promote functional recovery after stroke has been evaluated over the last two decades. Preclinical studies first established the potential for cultured neuronal cells derived from a teratocarcinoma cell line to be tested for safety and efficacy in the treatment of human stroke. In animal models of stroke that caused reproducible learning and motor deficits, injection of neuronal cells resulted in a return of learning behavior, retention time, and motor function. Clinical trials followed. Additional work with cells derived from a bone marrow neuroprogenitor line, fetal cortical stem cells, and other cell sources showed promise in preclinical studies and then these cells were tested in clinical studies. This report reviews the different biological repair approaches using cell implants, discusses clinical trial design and surgical methods, and the current state of research.<\/jats:p>","DOI":"10.1055\/s-0040-1722640","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T01:55:17Z","timestamp":1611798917000},"page":"101-106","source":"Crossref","is-referenced-by-count":3,"title":["Stem Cell Treatment for Ischemic Stroke Recovery"],"prefix":"10.1055","volume":"41","author":[{"given":"Douglas","family":"Kondziolka","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, NYU Langone Health, New York University, New York, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"issue":"01","key":"ref1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/scientificamerican0791-56","article-title":"Stroke therapy","volume":"265","author":"J A Zivin","year":"1991","journal-title":"Sci Am"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1006\/exnr.1997.6730","article-title":"Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats","volume":"149","author":"C V Borlongan","year":"1998","journal-title":"Exp Neurol"},{"issue":"04","key":"ref3","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1212\/WNL.59.4.514","article-title":"Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery","volume":"59","author":"Y Li","year":"2002","journal-title":"Neurology"},{"issue":"10","key":"ref4","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1161\/01.STR.0000141681.06735.9b","article-title":"Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume","volume":"35","author":"M Vendrame","year":"2004","journal-title":"Stroke"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1750-3639.1994.tb00814.x","article-title":"Functional recovery after brain infarction: plasticity and neural transplantation","volume":"4","author":"B B Johansson","year":"1994","journal-title":"Brain Pathol"},{"issue":"05","key":"ref6","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/0361-9230(93)90300-Z","article-title":"Striatal grafts in the ischemic striatum improve pallidal GABA release and passive avoidance","volume":"32","author":"H Nishino","year":"1993","journal-title":"Brain Res Bull"},{"issue":"02","key":"ref7","first-page":"147","article-title":"Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro","volume":"50","author":"P W Andrews","year":"1984","journal-title":"Lab Invest"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/jnr.490350603","article-title":"NTera 2 cells: a human cell line which displays characteristics expected of a human committed neuronal progenitor cell","volume":"35","author":"S J Pleasure","year":"1993","journal-title":"J Neurosci Res"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/cne.903570410","article-title":"Transplanted human neurons derived from a teratocarcinoma cell line (NTera-2) mature, integrate, and survive for over 1 year in the nude mouse brain","volume":"357","author":"S R Kleppner","year":"1995","journal-title":"J Comp Neurol"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1006\/exnr.1996.6393","article-title":"Transfectable and transplantable postmitotic human neurons: a potential \u201cplatform\u201d for gene therapy of nervous system diseases","volume":"144","author":"J Q Trojanowski","year":"1997","journal-title":"Exp Neurol"},{"key":"ref11","first-page":"291","article-title":"Embryonic spinal cord transplants enhance locomotor performance in spinalized newborn rats","volume":"72","author":"A Tessler","year":"1997","journal-title":"Adv Neurol"},{"issue":"01","key":"ref12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0149-7634(95)00063-1","article-title":"Neural transplantation as an experimental treatment modality for cerebral ischemia","volume":"21","author":"C V Borlongan","year":"1997","journal-title":"Neurosci Biobehav Rev"},{"issue":"12","key":"ref13","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1097\/00001756-199808240-00028","article-title":"Viability and survival of hNT neurons determine degree of functional recovery in grafted ischemic rats","volume":"9","author":"C V Borlongan","year":"1998","journal-title":"Neuroreport"},{"issue":"05","key":"ref14","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/0031-9384(95)00103-P","article-title":"Locomotor and passive avoidance deficits following occlusion of the middle cerebral artery","volume":"58","author":"C V Borlongan","year":"1995","journal-title":"Physiol Behav"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"5372","DOI":"10.1523\/JNEUROSCI.15-07-05372.1995","article-title":"Elevated body swing test: a new behavioral parameter for rats with 6-hydroxydopamine-induced hemiparkinsonism","volume":"15","author":"C V Borlongan","year":"1995","journal-title":"J Neurosci"},{"issue":"02","key":"ref16","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0306-4522(98)00610-1","article-title":"Neural transplantation of human neuroteratocarcinoma (hNT) neurons into ischemic rats. A quantitative dose-response analysis of cell survival and behavioral recovery","volume":"91","author":"S Saporta","year":"1999","journal-title":"Neuroscience"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1006\/exnr.1993.1136","article-title":"Recovery of function after spinal cord injury: mechanisms underlying transplant-mediated recovery of function differ after spinal cord injury in newborn and adult rats","volume":"123","author":"B S Bregman","year":"1993","journal-title":"Exp Neurol"},{"issue":"01","key":"ref18","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/cne.903390111","article-title":"Grafts of fetal central nervous system tissue rescue axotomized Clarke's nucleus neurons in adult and neonatal operates","volume":"339","author":"B T Himes","year":"1994","journal-title":"J Comp Neurol"},{"issue":"02","key":"ref19","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/cne.903070211","article-title":"Axonal projections between fetal spinal cord transplants and the adult rat spinal cord: a neuroanatomical tracing study of local interactions","volume":"307","author":"L B Jakeman","year":"1991","journal-title":"J Comp Neurol"},{"key":"ref20","first-page":"121","article-title":"Potential of neural \u201cstem-like\u201d cells for gene therapy and repair of the degenerating central nervous system","volume":"72","author":"E Y Snyder","year":"1997","journal-title":"Adv Neurol"},{"issue":"01","key":"ref21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/cne.902440107","article-title":"Neural tissue transplants rescue axotomized rubrospinal cells from retrograde death","volume":"244","author":"B S Bregman","year":"1986","journal-title":"J Comp Neurol"},{"issue":"03","key":"ref22","first-page":"586","article-title":"Serial [18F] fluorodeoxyglucose positron emission tomography after human neuronal implantation for stroke","volume":"49","author":"C C Meltzer","year":"2001","journal-title":"Neurosurgery"},{"issue":"04","key":"ref23","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/S0002-9440(10)62546-1","article-title":"Clonal human (hNT) neuron grafts for stroke therapy: neuropathology in a patient 27 months after implantation","volume":"160","author":"P T Nelson","year":"2002","journal-title":"Am J Pathol"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3171\/jns.2005.103.1.0038","article-title":"Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial","volume":"103","author":"D Kondziolka","year":"2005","journal-title":"J Neurosurg"},{"issue":"04","key":"ref25","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1212\/WNL.55.4.565","article-title":"Transplantation of cultured human neuronal cells for patients with stroke","volume":"55","author":"D Kondziolka","year":"2000","journal-title":"Neurology"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"749","DOI":"10.3727\/000000004783983350","article-title":"Evaluation of surgical techniques for neuronal cell transplantation used in patients with stroke","volume":"13","author":"D Kondziolka","year":"2004","journal-title":"Cell Transplant"},{"issue":"11","key":"ref27","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1161\/01.STR.25.11.2215","article-title":"The European Stroke Scale","volume":"25","author":"L Hantson","year":"1994","journal-title":"Stroke"},{"issue":"07","key":"ref28","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1161\/01.STR.20.7.864","article-title":"Measurements of acute cerebral infarction: a clinical examination scale","volume":"20","author":"T Brott","year":"1989","journal-title":"Stroke"},{"issue":"07","key":"ref29","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1212\/01.WNL.0000140700.44904.53","article-title":"Changes in cognitive function after neuronal cell transplantation for basal ganglia stroke","volume":"63","author":"C S Stilley","year":"2004","journal-title":"Neurology"},{"issue":"03","key":"ref30","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1227\/01.NEU.0000255346.25959.99","article-title":"Treatment of traumatic brain injury with a combination therapy of marrow stromal cells and atorvastatin in rats","volume":"60","author":"A Mahmood","year":"2007","journal-title":"Neurosurgery"},{"issue":"12","key":"ref31","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1097\/01.jnen.0000190068.03009.b5","article-title":"Behavioral and histological evaluation of a focal cerebral infarction rat model transplanted with neurons induced from bone marrow stromal cells","volume":"64","author":"T Mimura","year":"2005","journal-title":"J Neuropathol Exp Neurol"},{"issue":"12","key":"ref32","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1172\/JCI200420935","article-title":"Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation","volume":"113","author":"M Dezawa","year":"2004","journal-title":"J Clin Invest"},{"issue":"07","key":"ref33","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1161\/STROKEAHA.116.012995","article-title":"Clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: a phase 1\/2a study","volume":"47","author":"G K Steinberg","year":"2016","journal-title":"Stroke"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.3171\/2018.5.JNS173147","article-title":"Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow-derived mesenchymal stem cells (SB623): a phase 1\/2a study","volume":"131","author":"G K Steinberg","year":"2018","journal-title":"J Neurosurg"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0140-6736(16)30513-X","article-title":"Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a phase 1, first-in-man study","volume":"388","author":"D Kalladka","year":"2016","journal-title":"Lancet"},{"issue":"11","key":"ref36","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1002\/stem.3080","article-title":"Intravenous bone marrow mononuclear cells for acute ischemic stroke: safety, feasibility and effect size from a phase 1 clinical trial","volume":"37","author":"F S Vahidy","year":"2019","journal-title":"Stem Cells"},{"issue":"04","key":"ref37","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1097\/00006123-199910000-00001","article-title":"Restorative neurosurgery: opportunities for restoration of function in acquired, degenerative, and idiopathic neurological diseases","volume":"45","author":"T P Thompson","year":"1999","journal-title":"Neurosurgery"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1161\/STROKEAHA.114.007028","article-title":"Intravenous autologous bone marrow mono nuclear stern cell therapy for ischemic stroke: a multicentric radomized trial","volume":"45","author":"K Prasad","year":"2014","journal-title":"Stroke"}],"container-title":["Seminars in Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1722640.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T23:48:32Z","timestamp":1614037712000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1722640"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,27]]},"references-count":38,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2021,2,22]]},"published-print":{"date-parts":[[2021,2]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1722640","relation":{},"ISSN":["0271-8235","1098-9021"],"issn-type":[{"value":"0271-8235","type":"print"},{"value":"1098-9021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,27]]}}}