{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:10:49Z","timestamp":1790100649889,"version":"4.0.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T00:00:00Z","timestamp":1450742400000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"MEYS Kontact II","award":["LH12024"],"award-info":[{"award-number":["LH12024"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stem cell treatment provides a promising therapy for patients with spinal cord injury (SCI). However, the applied stem cells exert their effects in different manners that are dependent on the route used for administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the present study, we administered neural precursors derived from induced pluripotent stem cells (iPS-NPs) either intraspinally into the lesion center or intrathecally into the subarachnoid space of rats with a balloon-induced spinal cord compression lesion. Functional locomotor performance, cell survival, astrogliosis, axonal sprouting and the expression of endogenous neurotrophic growth factors were evaluated using behavioral tests (BBB, flat beam test, rotarod, plantar test), morphometric analysis, immunohistochemistry and qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both treatments facilitated the functional locomotor recovery of rats with SCI. iPS-NPs injected intraspinally survived well for 2\u00a0months and were positive for MAP2, while cells grafted intrathecally were undetectable at the site of administration or in the spinal cord tissue. Intraspinal implantation increased gray and white matter sparing and axonal sprouting and reduced astrogliosis, while intrathecal application resulted only in an improvement of white matter sparing and an increase in axonal sprouting, in parallel with no positive effect on the expression of endogenous neurotrophic growth factor genes or glial scar reduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Intrathecally grafted iPS-NPs had a moderate therapeutic benefit on SCI through a paracrine mechanism that does not require the cells to be present in the tissue; however, the extended survival of i.s. grafted cells in the spinal cord may promote long-term spinal cord tissue regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-015-0255-2","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T08:08:43Z","timestamp":1450771723000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats"],"prefix":"10.1186","volume":"6","author":[{"given":"Takashi","family":"Amemori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Ruzicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Romanyuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Jhanwar-Uniyal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Sykova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavla","family":"Jendelova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,22]]},"reference":[{"key":"255_CR1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1097\/MOT.0000000000000244","volume":"20","author":"MG Angelos","year":"2015","unstructured":"Angelos MG, Kaufman DS. Pluripotent stem cell applications for regenerative medicine. Curr Opin Organ Transplant. 2015;20:663\u201370.","journal-title":"Curr Opin Organ Transplant."},{"key":"255_CR2","doi-asserted-by":"crossref","unstructured":"Erceg S, Lukovic D, Moreno-Manzano V, Stojkovic M, Bhattacharya SS. Derivation of cerebellar neurons from human pluripotent stem cells. Curr Protoc Stem Cell Biol. 2012;Chapter 1:Unit 1H 5.","DOI":"10.1002\/9780470151808.sc01h05s20"},{"key":"255_CR3","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3390\/jcm4010193","volume":"4","author":"SI Hodgetts","year":"2015","unstructured":"Hodgetts SI, Edel M, Harvey AR. The state of play with iPSCs and spinal cord injury models. J Clin Med. 2015;4:193\u2013203.","journal-title":"J Clin Med."},{"key":"255_CR4","doi-asserted-by":"publisher","unstructured":"Jin X, Lin T, Xu Y. Stem cell therapy and immunological rejection in animal models. Curr Mol Pharmacol. 2015. doi:10.2174\/1874467208666150928153511.","DOI":"10.2174\/1874467208666150928153511"},{"key":"255_CR5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.4103\/1673-5374.150638","volume":"10","author":"CA Lee-Kubli","year":"2015","unstructured":"Lee-Kubli CA, Lu P. Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury. Neural Regen Res. 2015;10:10\u20136.","journal-title":"Neural Regen Res."},{"key":"255_CR6","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1002\/stem.1083","volume":"30","author":"Y Fujimoto","year":"2012","unstructured":"Fujimoto Y, Abematsu M, Falk A, Tsujimura K, Sanosaka T, Juliandi B, et al. Treatment of a mouse model of spinal cord injury by transplantation of human induced pluripotent stem cell-derived long-term self-renewing neuroepithelial-like stem cells. Stem Cells. 2012;30:1163\u201373.","journal-title":"Stem Cells."},{"key":"255_CR7","doi-asserted-by":"crossref","unstructured":"Nori S, Okada Y, Yasuda A, Tsuji O, Takahashi Y, Kobayashi Y, et al. Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc Natl Acad Sci USA. 2011;108:16825\u201330.","DOI":"10.1073\/pnas.1108077108"},{"key":"255_CR8","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1186\/s13287-015-0118-x","volume":"6","author":"J Oh","year":"2015","unstructured":"Oh J, Lee KI, Kim HT, You Y, Yoon do H, Song KY, et al. Human-induced pluripotent stem cells generated from intervertebral disc cells improve neurologic functions in spinal cord injury. Stem Cell Res Ther. 2015;6:125.","journal-title":"Stem Cell Res Ther"},{"key":"255_CR9","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.3727\/096368914X684042","volume":"24","author":"N Romanyuk","year":"2015","unstructured":"Romanyuk N, Amemori T, Turnovcova K, Prochazka P, Onteniente B, Sykova E, et al. Beneficial effect of human induced pluripotent stem cell-derived neural precursors in spinal cord injury repair. Cell Transplant. 2015;24:1781\u201397.","journal-title":"Cell Transplant."},{"key":"255_CR10","doi-asserted-by":"publisher","first-page":"2707","DOI":"10.1002\/cne.23578","volume":"522","author":"D Sareen","year":"2014","unstructured":"Sareen D, Gowing G, Sahabian A, Staggenborg K, Paradis R, Avalos P, et al. Human induced pluripotent stem cells are a novel source of neural progenitor cells (iNPCs) that migrate and integrate in the rodent spinal cord. J Comp Neurol. 2014;522:2707\u201328.","journal-title":"J Comp Neurol."},{"key":"255_CR11","doi-asserted-by":"publisher","first-page":"e0116933","DOI":"10.1371\/journal.pone.0116933","volume":"10","author":"AH All","year":"2015","unstructured":"All AH, Gharibani P, Gupta S, Bazley FA, Pashai N, Chou BK, et al. Early intervention for spinal cord injury with human induced pluripotent stem cells oligodendrocyte progenitors. PLoS One. 2015;10:e0116933.","journal-title":"PLoS One."},{"key":"255_CR12","doi-asserted-by":"publisher","first-page":"743","DOI":"10.5966\/sctm.2014-0236","volume":"4","author":"RP Salewski","year":"2015","unstructured":"Salewski RP, Mitchell RA, Li L, Shen C, Milekovskaia M, Nagy A, et al. Transplantation of induced pluripotent stem cell-derived neural stem cells mediate functional recovery following thoracic spinal cord injury through remyelination of axons. Stem Cells Transl Med. 2015;4:743\u201354.","journal-title":"Stem Cells Transl Med."},{"key":"255_CR13","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.expneurol.2015.03.031","volume":"269","author":"K Pajer","year":"2015","unstructured":"Pajer K, Nemes C, Berzsenyi S, Kovacs KA, Pirity MK, Pajenda G, et al. Grafted murine induced pluripotent stem cells prevent death of injured rat motoneurons otherwise destined to die. Exp Neurol. 2015;269:188\u2013201.","journal-title":"Exp Neurol."},{"key":"255_CR14","doi-asserted-by":"publisher","first-page":"12704","DOI":"10.1073\/pnas.0910106107","volume":"107","author":"O Tsuji","year":"2010","unstructured":"Tsuji O, Miura K, Okada Y, Fujiyoshi K, Mukaino M, Nagoshi N, et al. Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc Natl Acad Sci U S A. 2010;107:12704\u20139.","journal-title":"Proc Natl Acad Sci U S A."},{"key":"255_CR15","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1089\/neu.2006.23.55","volume":"23","author":"A Bakshi","year":"2006","unstructured":"Bakshi A, Barshinger AL, Swanger SA, Madhavani V, Shumsky JS, Neuhuber B, et al. Lumbar puncture delivery of bone marrow stromal cells in spinal cord contusion: a novel method for minimally invasive cell transplantation. J Neurotrauma. 2006;23:55\u201365.","journal-title":"J Neurotrauma."},{"key":"255_CR16","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1093\/icvts\/ivu021","volume":"18","author":"GI Judas","year":"2014","unstructured":"Judas GI, Ferreira SG, Simas R, Sannomiya P, Benicio A, da Silva LF, et al. Intrathecal injection of human umbilical cord blood stem cells attenuates spinal cord ischaemic compromise in rats. Interact Cardiovasc Thorac Surg. 2014;18:757\u201362.","journal-title":"Interact Cardiovasc Thorac Surg."},{"key":"255_CR17","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1097\/BRS.0b013e31819403ce","volume":"34","author":"C Paul","year":"2009","unstructured":"Paul C, Samdani AF, Betz RR, Fischer I, Neuhuber B. Grafting of human bone marrow stromal cells into spinal cord injury: a comparison of delivery methods. Spine. 2009;34:328\u201334.","journal-title":"Spine."},{"key":"255_CR18","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.3727\/096368912X657260","volume":"22","author":"V Volarevic","year":"2013","unstructured":"Volarevic V, Erceg S, Bhattacharya SS, Stojkovic P, Horner P, Stojkovic M. Stem cell-based therapy for spinal cord injury. Cell Transplant. 2013;22:1309\u201323.","journal-title":"Cell Transplant."},{"key":"255_CR19","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3109\/14653240903440103","volume":"12","author":"T Amemori","year":"2010","unstructured":"Amemori T, Jendelova P, Ruzickova K, Arboleda D, Sykova E. Co-transplantation of olfactory ensheathing glia and mesenchymal stromal cells does not have synergistic effects after spinal cord injury in the rat. Cytotherapy. 2010;12:212\u201325.","journal-title":"Cytotherapy."},{"key":"255_CR20","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1007\/s10571-011-9712-3","volume":"31","author":"D Arboleda","year":"2011","unstructured":"Arboleda D, Forostyak S, Jendelova P, Marekova D, Amemori T, Pivonkova H, et al. Transplantation of predifferentiated adipose-derived stromal cells for the treatment of spinal cord injury. Cell Mol Neurobiol. 2011;31:1113\u201322.","journal-title":"Cell Mol Neurobiol."},{"key":"255_CR21","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/scrt219","volume":"4","author":"T Amemori","year":"2013","unstructured":"Amemori T, Romanyuk N, Jendelova P, Herynek V, Turnovcova K, Prochazka P, et al. Human conditionally immortalized neural stem cells improve locomotor function after spinal cord injury in the rat. Stem Cell Res Ther. 2013;4:68.","journal-title":"Stem Cell Res Ther."},{"key":"255_CR22","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.3727\/096368912X653228","volume":"21","author":"J Polentes","year":"2012","unstructured":"Polentes J, Jendelova P, Cailleret M, Braun H, Romanyuk N, Tropel P, et al. Human induced pluripotent stem cells improve stroke outcome and reduce secondary degeneration in the recipient brain. Cell Transplant. 2012;21:2587\u2013602.","journal-title":"Cell Transplant."},{"key":"255_CR23","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/82881","volume":"4","author":"HM Bomze","year":"2001","unstructured":"Bomze HM, Bulsara KR, Iskandar BJ, Caroni P, Skene JH. Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nat Neurosci. 2001;4:38\u201343.","journal-title":"Nat Neurosci."},{"key":"255_CR24","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.jneumeth.2008.01.004","volume":"170","author":"ES da Costa","year":"2008","unstructured":"da Costa ES, Carvalho AL, Martinez AM, De-Ary-Pires B, Pires-Neto MA, de Ary-Pires R. Strapping the spinal cord: an innovative experimental model of CNS injury in rats. J Neurosci Methods. 2008;170:130\u20139.","journal-title":"J Neurosci Methods."},{"key":"255_CR25","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1089\/08977150152725687","volume":"18","author":"I Vanicky","year":"2001","unstructured":"Vanicky I, Urdzikova L, Saganova K, Cizkova D, Galik J. A simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat. J Neurotrauma. 2001;18:1399\u2013407.","journal-title":"J Neurotrauma."},{"key":"255_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/neu.1995.12.1","volume":"12","author":"DM Basso","year":"1995","unstructured":"Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12:1\u201321.","journal-title":"J Neurotrauma."},{"key":"255_CR27","doi-asserted-by":"publisher","unstructured":"Metz GA, Whishaw IQ. The ladder rung walking task: a scoring system and its practical application. J Vis Exp. 2009;28;1-4, doi: 10.3791\/1204.","DOI":"10.3791\/1204"},{"key":"255_CR28","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1093\/nar\/30.9.e36","volume":"30","author":"MW Pfaffl","year":"2002","unstructured":"Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30:e36.","journal-title":"Nucleic Acids Res."},{"key":"255_CR29","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1038\/sc.2011.46","volume":"49","author":"AJ Mothe","year":"2011","unstructured":"Mothe AJ, Bozkurt G, Catapano J, Zabojova J, Wang X, Keating A, et al. Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat. Spinal Cord. 2011;49:967\u201373.","journal-title":"Spinal Cord."},{"key":"255_CR30","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1089\/neu.2010.1413","volume":"28","author":"D Cizkova","year":"2011","unstructured":"Cizkova D, Novotna I, Slovinska L, Vanicky I, Jergova S, Rosocha J, et al. Repetitive intrathecal catheter delivery of bone marrow mesenchymal stromal cells improves functional recovery in a rat model of contusive spinal cord injury. J Neurotrauma. 2011;28:1951\u201361.","journal-title":"J Neurotrauma."},{"key":"255_CR31","doi-asserted-by":"publisher","first-page":"11275","DOI":"10.3390\/ijms150711275","volume":"15","author":"LM Urdzikova","year":"2014","unstructured":"Urdzikova LM, Ruzicka J, LaBagnara M, Karova K, Kubinova S, Jirakova K, et al. Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat. Int J Mol Sci. 2014;15:11275\u201393.","journal-title":"Int J Mol Sci."},{"key":"255_CR32","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1016\/j.cell.2012.08.020","volume":"150","author":"P Lu","year":"2012","unstructured":"Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, et al. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell. 2012;150:1264\u201373.","journal-title":"Cell."},{"key":"255_CR33","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.neuron.2014.07.014","volume":"83","author":"P Lu","year":"2014","unstructured":"Lu P, Woodruff G, Wang Y, Graham L, Hunt M, Wu D, et al. Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron. 2014;83:789\u201396.","journal-title":"Neuron."}],"container-title":["Stem Cell Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-015-0255-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-015-0255-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-015-0255-2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-015-0255-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T01:29:16Z","timestamp":1637026156000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-015-0255-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["255"],"URL":"https:\/\/doi.org\/10.1186\/s13287-015-0255-2","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]},"assertion":[{"value":"19 October 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"257"}}