{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:24:43Z","timestamp":1787063083046,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":229,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Human embryonic stem cell (hESC)\u2010derived multipotent mesenchymal stem cells (MMSCs) offer therapeutic potential for interstitial cystitis (IC); however, safety concerns, such as tumorigenicity from residual undifferentiated hESCs, must be thoroughly addressed. To address these concerns, we conducted comprehensive in vitro and in vivo safety assessments of clinical\u2010grade MMSCs. Flow cytometry, qRT\u2010PCR, and\/or RNA sequencing confirmed the absence of pluripotency markers, including\n                    <jats:italic>OCT3\/4<\/jats:italic>\n                    ,\n                    <jats:italic>TRA-1-60<\/jats:italic>\n                    ,\n                    <jats:italic>TRA-1-81<\/jats:italic>\n                    , and\n                    <jats:italic>NANOG<\/jats:italic>\n                    , in MMSCs. In good laboratory practice (GLP)\u2010compliant studies, BALB\/c\u2010\n                    <jats:italic>nu\/nu<\/jats:italic>\n                    immunodeficient mice received a single intra\u2010detrusor muscle injection of MMSCs. No adverse clinical signs or immune responses were observed at doses corresponding to up to 6 \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    cells in humans, the maximum feasible clinical dose based on body weight conversion. Furthermore, no tumor formation was detected for up to 52 weeks following either intra\u2010detrusor muscle or subcutaneous administration. Spiking studies showed teratoma formation only when undifferentiated hESCs exceeded 1%, supporting the absence of tumorigenic risk in the final MMSC product. Biodistribution analyses revealed that MMSCs remained localized at the injection site and were cleared from major organs within 10 days. These findings indicate that MMSCs contain no detectable hESCs within the sensitivity limits of the assays, exhibit no immunogenicity or tumorigenic potential, and are safe for intra\u2010detrusor muscle administration, supporting their clinical application as a cell\u2010based therapy for IC.\n                  <\/jats:p>","DOI":"10.1155\/sci\/5539154","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:27:07Z","timestamp":1787059627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Preclinical Safety Evaluation of Clinical\u2010Grade hESC\u2010Derived Multipotent Mesenchymal Stem Cells for Interstitial Cystitis"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3686-9432","authenticated-orcid":false,"given":"Jeong Min","family":"Shin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3671-1663","authenticated-orcid":false,"given":"Ah Reum","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2088-6395","authenticated-orcid":false,"given":"Dong Seol","family":"Gwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4545-0016","authenticated-orcid":false,"given":"Su Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-3807","authenticated-orcid":false,"given":"Jin Won","family":"Seo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6299-6876","authenticated-orcid":false,"given":"Eun-Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5623-4875","authenticated-orcid":false,"given":"Ki-Sung","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-7831","authenticated-orcid":false,"given":"Se-Pill","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7720-9009","authenticated-orcid":false,"given":"Hyung-Min","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/292154a0"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1145"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.08.020"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03376.x"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60663-3"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.8080\/1020200153819"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09330-x"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.27559"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szac065"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3122"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.095"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-020-00596-0"},{"key":"e_1_2_10_14_2","unstructured":"U.S. Food and Drug Administration (FDA) Characterization and Qualification of Cell Substrates and Other Biological Materials Used in the Production of Viral Vaccines for Infectious Disease Indications 2010 Guidance for Industry."},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/scrt39"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089546"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2020.112915"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(91)90377-R"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.10.3838"},{"key":"e_1_2_10_20_2","unstructured":"Korea Ministry of Food and Drug Safety Mixed Lymphocyte Reaction (MLR) Test for Mesenchymal Stem Cell Therapy Product 2012."},{"key":"e_1_2_10_21_2","unstructured":"U.S. Food and Drug Administration (FDA) Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers 2005 Guidance for Industry."},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2009.02.002"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2013.08.007"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003474"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368912X657837"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045532"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.16.9353"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.20138"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2007.0266"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-022-00608-y"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2003.038001"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-021-00643-1"},{"key":"e_1_2_10_33_2","first-page":"59","volume-title":"Common Spontaneous and Background Lesions in Laboratory Animals, Pathology of Toxicologists: Principles and Practices of Laboratory Animal Pathology for Study Personnel","author":"McInnes E.","year":"2017"},{"key":"e_1_2_10_34_2","first-page":"833","article-title":"Incidence and Pathological Features of Spontaneous Tumors in Athymic Nude Mice","volume":"39","author":"Sharkey F. E.","year":"1979","journal-title":"Cancer Res. Mar"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623319867053"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0016672300010168"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/372103a0"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.8.4473"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(89)90190-1"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)08101-5"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3002"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.12.7761"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803962"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.194"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szaf018"}],"container-title":["Stem Cells International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/sci\/5539154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/sci\/5539154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/sci\/5539154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:27:10Z","timestamp":1787059630000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/sci\/5539154"}},"subtitle":[],"editor":[{"given":"Satabdi","family":"Datta Choudhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/sci\/5539154"],"URL":"https:\/\/doi.org\/10.1155\/sci\/5539154","archive":["Portico"],"relation":{},"ISSN":["1687-966X","1687-9678"],"issn-type":[{"value":"1687-966X","type":"print"},{"value":"1687-9678","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"5539154"}}