{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,15]],"date-time":"2026-11-15T03:59:36Z","timestamp":1794715176348,"version":"4.9.1"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T00:00:00Z","timestamp":1504051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T00:00:00Z","timestamp":1504051200000},"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>Induced pluripotent stem cell-derived neural stem cells (iNSCs) have significant potential as an autologous, multifunctional cell therapy for stroke, which is the primary cause of long term disability in the United States and the second leading cause of death worldwide. Here we show that iNSC transplantation improves recovery through neuroprotective, regenerative, and cell replacement mechanisms in a novel ischemic pig stroke model. Longitudinal multiparametric magnetic resonance imaging (MRI) following iNSC therapy demonstrated reduced changes in white matter integrity, cerebral blood perfusion, and brain metabolism in the infarcted tissue. The observed tissue level recovery strongly correlated with decreased immune response, enhanced neuronal protection, and increased neurogenesis. iNSCs differentiated into neurons and oligodendrocytes with indication of long term integration. The robust recovery response to iNSC therapy in a translational pig stroke model with increased predictive potential strongly supports that iNSCs may be the critically needed therapeutic for human stroke patients.<\/jats:p>","DOI":"10.1038\/s41598-017-10406-x","type":"journal-article","created":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T15:13:30Z","timestamp":1503587610000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model"],"prefix":"10.1038","volume":"7","author":[{"given":"Emily W.","family":"Baker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon R.","family":"Platt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian W.","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison E.","family":"Grace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon P.","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylee Jo","family":"Duberstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth W.","family":"Howerth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly A.","family":"Kinder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve L.","family":"Stice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Hess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin D.","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,30]]},"reference":[{"key":"10406_CR1","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1161\/CIR.0000000000000152","volume":"131","author":"D Mozaffarian","year":"2015","unstructured":"Mozaffarian, D. et al. Heart disease and stroke statistics\u20132015 update: a report from the American Heart Association. Circulation \n                           131, e29\u2013322, doi:10.1161\/CIR.0000000000000152 (2015).","journal-title":"Circulation"},{"key":"10406_CR2","doi-asserted-by":"publisher","first-page":"465","DOI":"10.5114\/aoms.2011.23413","volume":"7","author":"SA Mousavi","year":"2011","unstructured":"Mousavi, S. A., Saadatnia, M., Khorvash, F., Hoseini, T. & Sariaslani, P. Evaluation of the neuroprotective effect of dextromethorphan in the acute phase of ischaemic stroke. Arch Med Sci \n                           7, 465\u2013469, doi:10.5114\/aoms.2011.23413 (2011).","journal-title":"Arch Med Sci"},{"key":"10406_CR3","doi-asserted-by":"publisher","unstructured":"Sharma, V. K. et al. Recanalization therapies in acute ischemic stroke: pharmacological agents, devices, and combinations. Stroke research and treatment \n                           2010, doi:10.4061\/2010\/672064 (2010).","DOI":"10.4061\/2010\/672064"},{"key":"10406_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s13012-016-0414-6","volume":"11","author":"CL Paul","year":"2016","unstructured":"Paul, C. L. et al. How can we improve stroke thrombolysis rates? A review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care. Implementation science: IS \n                           11, 51, doi:10.1186\/s13012-016-0414-6 (2016).","journal-title":"Implementation science: IS"},{"key":"10406_CR5","doi-asserted-by":"publisher","first-page":"2752","DOI":"10.1161\/01.STR.30.12.2752","volume":"30","author":"Stroke Therapy Academic Industry, R","year":"1999","unstructured":"Stroke Therapy Academic Industry, R. Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke; a journal of cerebral circulation \n                           30, 2752\u20132758 (1999).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"10406_CR6","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1161\/STROKEAHA.108.526863","volume":"40","author":"Stem Cell Therapies as an Emerging Paradigm in Stroke, P","year":"2009","unstructured":"Stem Cell Therapies as an Emerging Paradigm in Stroke, P. Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS): bridging basic and clinical science for cellular and neurogenic factor therapy in treating stroke. Stroke; a journal of cerebral circulation \n                           40, 510\u2013515, doi:10.1161\/STROKEAHA.108.526863 (2009).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"10406_CR7","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1161\/STROKEAHA.110.601914","volume":"42","author":"SI Savitz","year":"2011","unstructured":"Savitz, S. I. et al. Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II. Stroke; a journal of cerebral circulation \n                           42, 825\u2013829, doi:10.1161\/STROKEAHA.110.601914 (2011).","journal-title":"Stroke; a journal of cerebral circulation"},{"key":"10406_CR8","doi-asserted-by":"publisher","first-page":"4335","DOI":"10.1073\/pnas.0910012107","volume":"107","author":"BY Hu","year":"2010","unstructured":"Hu, B. Y. et al. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proceedings of the National Academy of Sciences of the United States of America \n                           107, 4335\u20134340, doi:10.1073\/pnas.0910012107 (2010).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10406_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/2040-7378-6-5","volume":"6","author":"SR Platt","year":"2014","unstructured":"Platt, S. R. et al. Development and characterization of a Yucatan miniature biomedical Pig permanent middle cerebral artery occlusion stroke model. Experimental & translational stroke medicine \n                           6, 5, doi:10.1186\/2040-7378-6-5 (2014).","journal-title":"Experimental & translational stroke medicine"},{"key":"10406_CR10","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.physbeh.2013.11.004","volume":"125","author":"KJ Duberstein","year":"2014","unstructured":"Duberstein, K. J. et al. Gait analysis in a pre- and post-ischemic stroke biomedical pig model. Physiology & behavior \n                           125, 8\u201316, doi:10.1016\/j.physbeh.2013.11.004 (2014).","journal-title":"Physiology & behavior"},{"key":"10406_CR11","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. 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