{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:46:29Z","timestamp":1789004789335,"version":"build-2803163510"},"reference-count":30,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T00:00:00Z","timestamp":1462406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p>\n                    Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC.sTRAIL. At first, we injected stereotactically low (1.2\u2009\u00d7\u200910\n                    <jats:sup>5<\/jats:sup>\n                    cells\/18\u2009\u03bcL), medium (2.4\u2009\u00d7\u200910\n                    <jats:sup>5<\/jats:sup>\n                    \/18\u2009\u03bcL), or high dose (3.6\u2009\u00d7\u200910\n                    <jats:sup>5<\/jats:sup>\n                    \/18\u2009\u03bcL) of hAT-MSC.sTRAIL into the brainstems of immunodeficient mice reflecting the plan of the future clinical trial. Local toxicity, systemic toxicity, secondary tumor formation, and biodistribution of hAT-MSC.sTRAIL were investigated. Next, presence of hAT-MSC.sTRAIL was confirmed in the brain and major organs at 4, 9, and 14 weeks in brainstem glioma-bearing mice. In the 15-week subchronic toxicity test, no serious adverse events in terms of body weight, food consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology were observed. In the 26-week tumorigenicity test, hAT-MSC.sTRAIL made no detectable tumors, whereas positive control U-87 MG cells made huge tumors in the brainstem. No remaining hAT-MSC.sTRAIL was observed in any organs examined, including the brainstem at 15 or 26 weeks. In brainstem glioma-bearing mice, injected hAT-MSC.sTRAIL was observed, but gradually decreased over time in the brain. The mRNA of human specific GAPDH and TRAIL was not detected in all major organs. These results indicate that the hAT-MSC.sTRAIL could be applicable to the future clinical trials in terms of biosafety.\n                  <\/jats:p>","DOI":"10.1089\/scd.2015.0324","type":"journal-article","created":{"date-parts":[[2016,5,6]],"date-time":"2016-05-06T02:25:32Z","timestamp":1462501532000},"page":"897-908","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Preclinical Biosafety Evaluation of Genetically Modified Human Adipose Tissue-Derived Mesenchymal Stem Cells for Clinical Applications to Brainstem Glioma"],"prefix":"10.1177","volume":"25","author":[{"given":"Seung Ah","family":"Choi","sequence":"first","affiliation":[{"name":"Seoul National University College of Medicine"},{"name":"Adolescent Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Won","family":"Yun","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeung Min","family":"Joo","sequence":"additional","affiliation":[{"name":"SAIHST"},{"name":"Samsung Biomedical Research Institute"},{"name":"Sungkyunkwan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yeoun","family":"Lee","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"},{"name":"Seoul National University College of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pil Ae","family":"Kwak","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"},{"name":"Adolescent Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"},{"name":"SAIHST"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Ran","family":"You","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euna","family":"Kwon","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Chang","family":"Wang","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hoon","family":"Phi","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"},{"name":"Adolescent Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong-Cheol","family":"Kang","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute"},{"name":"Seoul National University College of Medicine"},{"name":"Seoul National University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ki","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine"},{"name":"Adolescent Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,5,5]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0451"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302276"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1874"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.6.2833"},{"key":"e_1_3_3_6_2","first-page":"1162","article-title":"Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells","volume":"61","author":"Hao C","year":"2001","unstructured":"Hao C, , Beguinot F, , Condorelli G, , Trencia A, , Van Meir EG, , Yong VW, et al. (2001). Induction and intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediated apotosis in human malignant glioma cells. Cancer Res, 61:1162\u20131170.","journal-title":"Cancer Res"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.1.221"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90057-8"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noq147"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1416"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207232"},{"key":"e_1_3_3_12_2","first-page":"1362","article-title":"Direct stimulation of apoptotic signaling by soluble Apo2l\/tumor necrosis factor-related apoptosis-inducing ligand leads to selective killing of glioma cells","volume":"7","author":"Pollack IF","year":"2001","unstructured":"Pollack IF, , Erff M, and Ashkenazi A. (2001). Direct stimulation of apoptotic signaling by soluble Apo2l\/tumor necrosis factor-related apoptosis-inducing ligand leads to selective killing of glioma cells. Clin Cancer Res, 7:1362\u20131369.","journal-title":"Clin Cancer Res"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(98)00409-8"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2015.25"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-011-0796-x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00468.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2012-0018"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-011-0645-6"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-014-0371-2"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v7.i1.126"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e31825ca05f"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-9574LSF"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btf877"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.2202\/1544-6115.1585"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)82000-6"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0438"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0620"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4630"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2013.03.005"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2665"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0248"}],"container-title":["Stem Cells and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/scd.2015.0324","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/scd.2015.0324","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/scd.2015.0324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:39:28Z","timestamp":1779694768000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/scd.2015.0324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,5]]},"references-count":30,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1089\/scd.2015.0324"],"URL":"https:\/\/doi.org\/10.1089\/scd.2015.0324","relation":{},"ISSN":["1547-3287","1557-8534"],"issn-type":[{"value":"1547-3287","type":"print"},{"value":"1557-8534","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,5]]}}}