{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:42:21Z","timestamp":1790754141209,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To evaluate the preclinical studies using NSCs transplantation therapy for experimental ischemic stroke and determine the effect size of NSCs therapy and the correlations between different clinical measures. We firstly searched literatures to identify studies of NSCs therapy in animal cerebral ischemia models and then calculated the quality score of studies, assessed the effect size of NSCs therapy relative to behavioral and histologic endpoints by meta-analysis. A total of 37 studies and 54 independent treated interventions were used for systematic review and meta-analysis. The median quality score was 5 of 10. 36 studies (53 intervention arms) reported functional outcome, 22 studies (34 intervention arms) reported structural outcome. After adjusted by subgroup and sensitivity analysis, the mean effect sizes were improved by 1.35 for mNSS, 1.84 for rotarod test, 0.61 for cylinder test and 0.84 for infarct volume. Furthermore, effect size had a certain interaction with clinical variables, for example early NSCs therapy <jats:italic>etc.<\/jats:italic> In this preclinical studies, we demonstrated that transplanted NSCs significantly improved outcomes (both functional and structural outcome) in ischemic stroke. It is suggested that future preclinical animal model studies of stroke should improve study quality validity and reduce potentially confounded publication bias.<\/jats:p>","DOI":"10.1038\/srep32291","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T09:14:26Z","timestamp":1472030066000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Meta-Analysis and Systematic Review of Neural Stem Cells therapy for experimental ischemia stroke in preclinical studies"],"prefix":"10.1038","volume":"6","author":[{"given":"Lukui","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchun","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,24]]},"reference":[{"key":"BFsrep32291_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0140-6736(14)61682-2","volume":"385","author":"GBD Mortality","year":"2015","unstructured":"Mortality, G. B. D. & Causes of Death, C. Global, regional and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385, 117\u2013171 (2015).","journal-title":"Lancet"},{"key":"BFsrep32291_CR2","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/j.1747-4949.2008.00218.x","volume":"3","author":"C Wang","year":"2008","unstructured":"Wang, C. et al. Stroke care development in Mainland China: past, present and future. Int J Stroke 3, 288\u2013289 (2008).","journal-title":"Int J Stroke"},{"key":"BFsrep32291_CR3","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1007\/s12975-010-0047-z","volume":"1","author":"M Ning","year":"2010","unstructured":"Ning, M. et al. Proteomic Protease Substrate Profiling of tPA Treatment in Acute Ischemic Stroke Patients: A Step Toward Individualizing Thrombolytic Therapy at the Bedside. Transl Stroke Res 1, 268\u2013275 (2010).","journal-title":"Transl Stroke Res"},{"key":"BFsrep32291_CR4","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1161\/STROKEAHA.111.635334","volume":"43","author":"SC Cramer","year":"2012","unstructured":"Cramer, S. C. et al. Organization of a United States county system for comprehensive acute stroke care. Stroke 43, 1089\u20131093 (2012).","journal-title":"Stroke"},{"key":"BFsrep32291_CR5","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1002\/ana.21412","volume":"63","author":"SC Cramer","year":"2008","unstructured":"Cramer, S. C. Repairing the human brain after stroke. II. Restorative therapies. Ann Neurol 63, 549\u2013560 (2008).","journal-title":"Ann Neurol"},{"key":"BFsrep32291_CR6","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/3473","volume":"16","author":"JD Flax","year":"1998","unstructured":"Flax, J. D. et al. Engraftable human neural stem cells respond to developmental cues, replace neurons and express foreign genes. Nat Biotechnol 16, 1033\u20131039 (1998).","journal-title":"Nat Biotechnol"},{"key":"BFsrep32291_CR7","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/nrn1908","volume":"7","author":"G Martino","year":"2006","unstructured":"Martino, G. & Pluchino, S. The therapeutic potential of neural stem cells. Nat Rev Neurosci 7, 395\u2013406 (2006).","journal-title":"Nat Rev Neurosci"},{"key":"BFsrep32291_CR8","doi-asserted-by":"publisher","first-page":"90","DOI":"10.4068\/cmj.2011.47.2.90","volume":"47","author":"MC Lee","year":"2011","unstructured":"Lee, M. C. et al. Stem cell dynamics in an experimental model of stroke. Chonnam Med J 47, 90\u201398 (2011).","journal-title":"Chonnam Med J"},{"key":"BFsrep32291_CR9","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2217\/17460751.2.1.69","volume":"2","author":"SL Minger","year":"2007","unstructured":"Minger, S. L. et al. Endogenous neurogenesis in the human brain following cerebral infarction. Regen Med 2, 69\u201374 (2007).","journal-title":"Regen Med"},{"key":"BFsrep32291_CR10","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1152\/physrev.00032.2010","volume":"91","author":"G Martino","year":"2011","unstructured":"Martino, G., Pluchino, S., Bonfanti, L. & Schwartz, M. Brain regeneration in physiology and pathology: the immune signature driving therapeutic plasticity of neural stem cells. Physiol Rev 91, 1281\u20131304 (2011).","journal-title":"Physiol Rev"},{"key":"BFsrep32291_CR11","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1038\/nbt.2993","volume":"32","author":"AV Naumova","year":"2014","unstructured":"Naumova, A. V., Modo, M., Moore, A., Murry, C. E. & Frank, J. A. Clinical imaging in regenerative medicine. Nat Biotechnol 32, 804\u2013818 (2014).","journal-title":"Nat Biotechnol"},{"key":"BFsrep32291_CR12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.expneurol.2013.03.009","volume":"260","author":"E Giusto","year":"2014","unstructured":"Giusto, E., Donega, M., Cossetti, C. & Pluchino, S. Neuro-immune interactions of neural stem cell transplants: from animal disease models to human trials. Exp Neurol 260, 19\u201332 (2014).","journal-title":"Exp Neurol"},{"key":"BFsrep32291_CR13","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nrn1829","volume":"7","author":"FJ Muller","year":"2006","unstructured":"Muller, F. J., Snyder, E. Y. & Loring, J. F. Gene therapy: can neural stem cells deliver? Nature Reviews Neuroscience 7, 75\u201384 (2006).","journal-title":"Nature Reviews Neuroscience"},{"key":"BFsrep32291_CR14","doi-asserted-by":"crossref","unstructured":"Nordmann, A. J., Kasenda, B. & Briel, M. Meta-analyses: what they can and cannot do. Swiss Medical Weekly 142 (2012).","DOI":"10.4414\/smw.2012.13518"},{"key":"BFsrep32291_CR15","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1177\/0141076807100012020","volume":"100","author":"K O\u2019Rourke","year":"2007","unstructured":"O\u2019Rourke, K. An historical perspective on meta-analysis: dealing quantitatively with varying study results. Journal Of the Royal Society Of Medicine 100, 579\u2013582 (2007).","journal-title":"Journal Of the Royal Society Of Medicine"},{"key":"BFsrep32291_CR16","doi-asserted-by":"publisher","first-page":"431","DOI":"10.3949\/ccjm.75.6.431","volume":"75","author":"E Walker","year":"2008","unstructured":"Walker, E., Hernandez, A. V. & Kattan, M. W. Meta-analysis: Its strengths and limitations. Cleve Clin J Med 75, 431\u2013439 (2008).","journal-title":"Cleve Clin J Med"},{"key":"BFsrep32291_CR17","doi-asserted-by":"publisher","first-page":"2244","DOI":"10.1161\/STROKEAHA.108.541128","volume":"40","author":"M Fisher","year":"2009","unstructured":"Fisher, M. et al. Update of the Stroke Therapy Academic Industry Roundtable Preclinical Recommendations. Stroke 40, 2244\u20132250 (2009).","journal-title":"Stroke"},{"key":"BFsrep32291_CR18","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nature11556","volume":"490","author":"SC Landis","year":"2012","unstructured":"Landis, S. C. et al. A call for transparent reporting to optimize the predictive value of preclinical research. Nature 490, 187\u2013191 (2012).","journal-title":"Nature"},{"key":"BFsrep32291_CR19","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1161\/STROKEAHA.107.498725","volume":"39","author":"NA Crossley","year":"2008","unstructured":"Crossley, N. A. et al. Empirical evidence of bias in the design of experimental stroke studies-A metaepidemiologic approach. Stroke 39, 929\u2013934 (2008).","journal-title":"Stroke"},{"key":"BFsrep32291_CR20","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1161\/01.STR.0000125719.25853.20","volume":"35","author":"MR Macleod","year":"2004","unstructured":"Macleod, M. R., O\u2019Collins, T., Howells, D. W. & Donnan, G. A. Pooling of animal experimental data reveals influence of study design and publication bias. Stroke 35, 1203\u20131208 (2004).","journal-title":"Stroke"},{"key":"BFsrep32291_CR21","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/j.1747-4949.2012.00797.x","volume":"7","author":"JS Lees","year":"2012","unstructured":"Lees, J. S. et al. Stem cell-based therapy for experimental stroke: A systematic review and meta-analysis. International Journal Of Stroke 7, 582\u2013588 (2012).","journal-title":"International Journal Of Stroke"},{"key":"BFsrep32291_CR22","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1212\/WNL.0000000000000278","volume":"82","author":"Q Vu","year":"2014","unstructured":"Vu, Q., Xie, K., Eckert, M., Zhao, W. A. & Cramer, S. C. Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke. Neurology 82, 1277\u20131286 (2014).","journal-title":"Neurology"},{"key":"BFsrep32291_CR23","doi-asserted-by":"crossref","unstructured":"Hao, L. et al. Stem Cell-Based Therapies for Ischemic Stroke. Biomed Research International (2014).","DOI":"10.1155\/2014\/468748"},{"key":"BFsrep32291_CR24","doi-asserted-by":"publisher","first-page":"63","DOI":"10.15283\/ijsc.2014.7.2.63","volume":"7","author":"H Jeong","year":"2014","unstructured":"Jeong, H. et al. Efficacy and safety of stem cell therapies for patients with stroke: a systematic review and single arm meta-analysis. Int J Stem Cells 7, 63\u201369 (2014).","journal-title":"Int J Stem Cells"},{"key":"BFsrep32291_CR25","doi-asserted-by":"crossref","unstructured":"Nucci, L. P. et al. Stem cells labeled with superparamagnetic iron oxide nanoparticles in a preclinical model of cerebral ischemia: a systematic review with meta-analysis. Stem Cell Research & Therapy 6 (2015).","DOI":"10.1186\/s13287-015-0015-3"},{"key":"BFsrep32291_CR26","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1002\/ana.20741","volume":"59","author":"VE O\u2019Collins","year":"2006","unstructured":"O\u2019Collins, V. E. et al. 1,026 experimental treatments in acute stroke. Annals Of Neurology 59, 467\u2013477 (2006).","journal-title":"Annals Of Neurology"},{"key":"BFsrep32291_CR27","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1001\/jama.1995.03520290060030","volume":"273","author":"KF Schulz","year":"1995","unstructured":"Schulz, K. F., Chalmers, I., Hayes, R. J. & Altman, D. G. Empirical-Evidence Of Bias-Dimensions Of Methodological Quality Associated with Estimates of Treatment Effects In Controlled Trials. Jama-Journal Of the American Medical Association 273, 408\u2013412 (1995).","journal-title":"Jama-Journal Of the American Medical Association"},{"key":"BFsrep32291_CR28","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1089\/scd.2009.0271","volume":"19","author":"M Janowski","year":"2010","unstructured":"Janowski, M., Walczak, P. & Date, I. Intravenous Route of Cell Delivery for Treatment of Neurological Disorders: A Meta-Analysis of Preclinical Results. Stem Cells And Development 19, 5\u201316 (2010).","journal-title":"Stem Cells And Development"},{"key":"BFsrep32291_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.brainres.2009.05.100","volume":"1284","author":"B Chen","year":"2009","unstructured":"Chen, B. et al. Neuroprotective effect of grafting GDNF gene-modified neural stem cells on cerebral ischemia in rats. Brain Research 1284, 1\u201311 (2009).","journal-title":"Brain Research"},{"key":"BFsrep32291_CR30","doi-asserted-by":"crossref","unstructured":"Sena, E. S., van der Worp, H. B., Bath, P. M. W., Howells, D. W. & Macleod, M. R. Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy. Plos Biology 8 (2010).","DOI":"10.1371\/journal.pbio.1000344"},{"key":"BFsrep32291_CR31","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/S0002-9440(10)62546-1","volume":"160","author":"PT Nelson","year":"2002","unstructured":"Nelson, P. T. et al. Clonal human (hNT) neuron grafts for stroke therapy-Neuropathology in a patient 27 months after implantation. American Journal Of Pathology 160, 1201\u20131206 (2002).","journal-title":"American Journal Of Pathology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep32291","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T22:38:35Z","timestamp":1672871915000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep32291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,24]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,10,17]]}},"alternative-id":["BFsrep32291"],"URL":"https:\/\/doi.org\/10.1038\/srep32291","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,24]]},"assertion":[{"value":"7 April 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32291"}}