{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:35:35Z","timestamp":1791920135569,"version":"4.3.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Korea Healthcare Technology R&D Project of the Ministry for Health & Welfare Affairs, Republic of Korea","award":["HI10C1673"],"award-info":[{"award-number":["HI10C1673"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Stem cell therapy is an emerging alternative therapeutic or disease-modifying strategy for amyotrophic lateral sclerosis (ALS). The aim of this open-label phase I clinical trial was to evaluate the safety of two repeated intrathecal injections of autologous bone marrow (BM)-derived mesenchymal stromal cells (MSCs) in ALS patients. Eight patients with definite or probable ALS were enrolled. After a 3-month lead-in period, autologous MSCs were isolated two times from the BM at an interval of 26 days and were then expanded in vitro for 28 days and suspended in autologous cerebrospinal fluid. Of the 8 patients, 7 received 2 intrathecal injections of autologous MSCs (1 \u00d7 106 cells per kg) 26 days apart. Clinical or laboratory measurements were recorded to evaluate the safety 12 months after the first MSC injection. The ALS Functional Rating Scale-Revised (ALSFRS-R), the Appel ALS score, and forced vital capacity were used to evaluate the patients' disease status. One patient died before treatment and was withdrawn from the study. With the exception of that patient, no serious adverse events were observed during the 12-month follow-up period. Most of the adverse events were self-limited or subsided after supportive treatment within 4 days. Decline in the ALSFRS-R score was not accelerated during the 6-month follow-up period. Two repeated intrathecal injections of autologous MSCs were safe and feasible throughout the duration of the 12-month follow-up period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Stem cell therapy is an emerging alternative therapeutic or disease-modifying strategy for amyotrophic lateral sclerosis (ALS). To the authors' best knowledge, there are no clinical trials to evaluate the safety of repeated intrathecal injections of autologous bone marrow mesenchymal stromal cells in ALS. After the clinical trial (phase I\/II) was conducted, the stem cell (HYNR-CS, NEURONATA-R) was included in the revision of the regulations on orphan drug designation (number 160; December 31, 2013) and approved as a New Drug Application (Department of Cell and Gene Therapy 233; July 30, 2014) by the Korean Food and Drug Administration. The phase II trial is expected to be reported later.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.5966\/sctm.2014-0212","type":"journal-article","created":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T21:11:56Z","timestamp":1430514716000},"page":"590-597","source":"Crossref","is-referenced-by-count":161,"title":["Phase I Trial of Repeated Intrathecal Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis"],"prefix":"10.1093","volume":"4","author":[{"given":"Ki-Wook","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Neurology, College of Medicine, Hanyang University Hospital, Seoul, Republic of Korea"},{"name":"Cell Therapy Center for Neurologic Disorders, Hanyang University Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanil","family":"Moon","sequence":"additional","affiliation":[{"name":"Cell Therapy Center for Neurologic Disorders, Hanyang University Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Hanyang University Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-il","family":"Oh","sequence":"additional","affiliation":[{"name":"Cell Therapy Center for Neurologic Disorders, Hanyang University Hospital, Seoul, Republic of Korea"},{"name":"Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinseok","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Hanyang University Hospital, Seoul, Republic of Korea"},{"name":"Cell Therapy Center for Neurologic Disorders, Hanyang University Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Bioengineering Institute, Corestem Inc., Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Young","family":"Chang","sequence":"additional","affiliation":[{"name":"Bioengineering Institute, Corestem Inc., Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Suk","family":"Kim","sequence":"additional","affiliation":[{"name":"Bioengineering Institute, Corestem Inc., Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Hanyang University Hospital, Seoul, Republic of Korea"},{"name":"Cell Therapy Center for Neurologic Disorders, Hanyang University Hospital, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,5,1]]},"reference":[{"key":"2021122704235337700_R1","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1056\/NEJM200105313442207","article-title":"Amyotrophic lateral sclerosis","volume":"344","author":"Rowland","year":"2001","journal-title":"N Engl J Med"},{"key":"2021122704235337700_R2","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1016\/S0140-6736(07)60944-1","article-title":"Amyotrophic lateral sclerosis","volume":"369","author":"Mitchell","year":"2007","journal-title":"Lancet"},{"key":"2021122704235337700_R3","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3109\/14653249.2011.613929","article-title":"Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: A long-term safety study","volume":"14","author":"Mazzini","year":"2012","journal-title":"Cytotherapy"},{"key":"2021122704235337700_R4","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/stem.1079","article-title":"Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: Results of a phase I trial in 12 patients","volume":"30","author":"Glass","year":"2012","journal-title":"Stem Cells"},{"key":"2021122704235337700_R5","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1089\/152581601317211015","article-title":"Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis","volume":"10","author":"Janson","year":"2001","journal-title":"J Hematother Stem Cell Res"},{"key":"2021122704235337700_R6","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.3727\/096368911X582769","article-title":"Stem cell transplantation in amyotrophic lateral sclerosis patients: Methodological approach, safety, and feasibility","volume":"21","author":"Mart\u00ednez","year":"2012","journal-title":"Cell Transplant"},{"key":"2021122704235337700_R7","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/jcb.20886","article-title":"Mesenchymal stem cells as trophic mediators","volume":"98","author":"Caplan","year":"2006","journal-title":"J Cell Biochem"},{"key":"2021122704235337700_R8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1089\/scd.2008.0040","article-title":"Erythropoietin increases the motility of human bone marrow-multipotent stromal cells (hBM-MSCs) and enhances the production of neurotrophic factors from hBM-MSCs","volume":"18","author":"Koh","year":"2009","journal-title":"Stem Cells Dev"},{"key":"2021122704235337700_R9","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/stem.269","article-title":"Mesenchymal stromal cells: Current understanding and clinical status","volume":"28","author":"Salem","year":"2010","journal-title":"Stem Cells"},{"key":"2021122704235337700_R10","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1002\/jcb.23119","article-title":"Allogeneic mesenchymal stem cells: Agents of immune modulation","volume":"112","author":"English","year":"2011","journal-title":"J Cell Biochem"},{"key":"2021122704235337700_R11","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.molmed.2011.10.004","article-title":"The immunomodulatory capacity of mesenchymal stem cells","volume":"18","author":"Gebler","year":"2012","journal-title":"Trends Mol Med"},{"key":"2021122704235337700_R12","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.stem.2012.05.015","article-title":"Mesenchymal stromal cells: New directions","volume":"10","author":"Keating","year":"2012","journal-title":"Cell Stem Cell"},{"key":"2021122704235337700_R13","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.neulet.2009.10.074","article-title":"Dose-dependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice","volume":"468","author":"Kim","year":"2010","journal-title":"Neurosci Lett"},{"key":"2021122704235337700_R14","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/14653240902806986","article-title":"Multiple administrations of human marrow stromal cells through cerebrospinal fluid prolong survival in a transgenic mouse model of amyotrophic lateral sclerosis","volume":"11","author":"Zhang","year":"2009","journal-title":"Cytotherapy"},{"key":"2021122704235337700_R15","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jns.2011.08.036","article-title":"Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis","volume":"313","author":"Harris","year":"2012","journal-title":"J Neurol Sci"},{"key":"2021122704235337700_R16","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1001\/archneurol.2010.248","article-title":"Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis","volume":"67","author":"Karussis","year":"2010","journal-title":"Arch Neurol"},{"key":"2021122704235337700_R17","doi-asserted-by":"crossref","first-page":"465","DOI":"10.4103\/0028-3886.103185","article-title":"Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: A pilot study","volume":"60","author":"Prabhakar","year":"2012","journal-title":"Neurol India"},{"key":"2021122704235337700_R18","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1002\/stem.1770","article-title":"Biological markers of mesenchymal stromal cells as predictors of response to autologous stem cell transplantation in patients with amyotrophic lateral sclerosis: An investigator-initiated trial and in vivo study","volume":"32","author":"Kim","year":"2014","journal-title":"Stem Cells"},{"key":"2021122704235337700_R19","first-page":"163","article-title":"Efficacy and safety of autologous bone marrow-derived mesenchymal stem cell treatment in patients with amyotrophic lateral sclerosis","volume":"27","author":"Kim","year":"2009","journal-title":"J Korean Neurol Assoc"},{"key":"2021122704235337700_R20","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/146608200300079536","article-title":"El Escorial revisited: Revised criteria for the diagnosis of amyotrophic lateral sclerosis","volume":"1","author":"Brooks","year":"2000","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"key":"2021122704235337700_R21","doi-asserted-by":"crossref","first-page":"781","DOI":"10.7326\/0003-4819-141-10-200411160-00009","article-title":"Better reporting of harms in randomized trials: An extension of the CONSORT statement","volume":"141","author":"Ioannidis","year":"2004","journal-title":"Ann Intern Med"},{"key":"2021122704235337700_R22","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S1053-4296(03)00031-6","article-title":"CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment","volume":"13","author":"Trotti","year":"2003","journal-title":"Semin Radiat Oncol"},{"key":"2021122704235337700_R23","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.4155\/cli.11.127","article-title":"New considerations in the design of clinical trials for amyotrophic lateral sclerosis","volume":"1","author":"Berry","year":"2011","journal-title":"Clin Investig (Lond)"},{"key":"2021122704235337700_R24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.neulet.2014.05.001","article-title":"Erythropoietin modulates the immune-inflammatory response of a SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS)","volume":"574","author":"Noh","year":"2014","journal-title":"Neurosci Lett"},{"key":"2021122704235337700_R25","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1093\/brain\/awr074","article-title":"Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis","volume":"134","author":"Beers","year":"2011","journal-title":"Brain"},{"key":"2021122704235337700_R26","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/emmm.201201544","article-title":"Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival","volume":"5","author":"Henkel","year":"2013","journal-title":"EMBO Mol Med"},{"key":"2021122704235337700_R27","doi-asserted-by":"crossref","DOI":"10.1111\/jnc.12814","article-title":"The immunomodulatory effects of human mesenchymal stem cells on peripheral blood mononuclear cells in ALS patients","author":"Kwon","year":"2014","journal-title":"J Neurochem"},{"key":"2021122704235337700_R28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1741-7015-9-52","article-title":"Clinical trials for stem cell therapies","volume":"9","author":"Trounson","year":"2011","journal-title":"BMC Med"},{"key":"2021122704235337700_R29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/jcp.20959","article-title":"From the laboratory bench to the patient's bedside: An update on clinical trials with mesenchymal stem cells","volume":"211","author":"Giordano","year":"2007","journal-title":"J Cell Physiol"},{"key":"2021122704235337700_R30","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1465-3249(05)70787-8","article-title":"Mesenchymal stem cells: Progress toward promise","volume":"7","author":"Le Blanc","year":"2005","journal-title":"Cytotherapy"},{"key":"2021122704235337700_R31","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.expneurol.2009.08.007","article-title":"Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial","volume":"223","author":"Mazzini","year":"2010","journal-title":"Exp Neurol"},{"key":"2021122704235337700_R32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1080\/14653240802644651","article-title":"Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients","volume":"11","author":"Martinez","year":"2009","journal-title":"Cytotherapy"},{"key":"2021122704235337700_R33","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1212\/01.wnl.0000327668.43541.22","article-title":"Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis","volume":"71","author":"Appel","year":"2008","journal-title":"Neurology"},{"key":"2021122704235337700_R34","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/mus.20951","article-title":"Pilot study of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells in amyotrophic lateral sclerosis (ALS)","volume":"37","author":"Cashman","year":"2008","journal-title":"Muscle Nerve"},{"key":"2021122704235337700_R35","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/clpt.2010.44","article-title":"Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis","volume":"87","author":"Rice","year":"2010","journal-title":"Clin Pharmacol Ther"},{"issue":"suppl 1","key":"2021122704235337700_R36","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.3727\/096368912X633789","article-title":"Olfactory ensheathing cell neurorestorotherapy for amyotrophic lateral sclerosis patients: Benefits from multiple transplantations","volume":"21","author":"Chen","year":"2012","journal-title":"Cell Transplant"},{"key":"2021122704235337700_R37","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.expneurol.2008.07.011","article-title":"A novel cell transplantation protocol and its application to an ALS mouse model","volume":"213","author":"Morita","year":"2008","journal-title":"Exp Neurol"},{"key":"2021122704235337700_R38","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1136\/jnnp-2013-305770","article-title":"Does surgery accelerate progression of amyotrophic lateral sclerosis?","volume":"85","author":"Pinto","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2021122704235337700_R39","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1161\/CIRCRESAHA.108.187724","article-title":"Fate of culture-expanded mesenchymal stem cells in the microvasculature: In vivo observations of cell kinetics","volume":"104","author":"Toma","year":"2009","journal-title":"Circ Res"},{"key":"2021122704235337700_R40","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.stem.2009.05.003","article-title":"Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6","volume":"5","author":"Lee","year":"2009","journal-title":"Cell Stem Cell"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2014-0212","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2014-0212","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/4\/6\/590\/41864800\/stcltm_4_6_590.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/4\/6\/590\/41864800\/stcltm_4_6_590.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T21:49:03Z","timestamp":1642542543000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/4\/6\/590-597\/6397333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,1]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,5,1]]},"published-print":{"date-parts":[[2015,6,1]]}},"URL":"https:\/\/doi.org\/10.5966\/sctm.2014-0212","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,6,1]]},"published":{"date-parts":[[2015,5,1]]}}}