{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:07:40Z","timestamp":1758758860529,"version":"3.44.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Basic Science Research Program"},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009122","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2023R1A2C2003808","2019R1A2C1002526","2020R1I1A1A01073545","RS202400347173"],"award-info":[{"award-number":["2023R1A2C2003808","2019R1A2C1002526","2020R1I1A1A01073545","RS202400347173"]}],"id":[{"id":"10.13039\/100009122","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Three-dimensional (3D)-cultured tonsil-derived mesenchymal stem cells (TMSCs) show high therapeutic efficacy in murine colitis. We evaluated the in vivo localization and formation of 3D-TMSCs using electron microscopy. Mice with dextran sulfate sodium-induced chronic colitis received intraperitoneal injections of 3D-TMSCs. The formation and localization of TMSC aggregates in the peritoneal cavity were assessed by immunofluorescence and electron microscopy. In mice treated with 3D-TMSCs, white spherical aggregates attached to the peritoneal cavity were observed. Immunofluorescence staining revealed the co-localization of human-origin TMSCs and mouse immune cells within these aggregates. The presence of human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) confirmed the presence of human-origin TMSCs in the aggregates. Electron microscopy revealed that 3D-TMSCs were covered with mouse immune cells. The presence of pseudopodia and microvilli facilitated cell-to-cell connections, indicating a complex integrated structure rather than a mere collection of TMSCs. After 15 days, rough endoplasmic reticulum and mitochondria were identified within the cytoplasm of the TMSCs. Prominent autophagosomes and extracellular vesicles were observed within the intraperitoneal 3D-TMSC aggregates. These findings underscore the viability and paracrine effects of 3D-TMSCs and support their potential as an advanced therapeutic option for treating inflammatory bowel disease.<\/jats:p>","DOI":"10.1093\/mam\/ozae135","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T06:28:08Z","timestamp":1758695288000},"source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Morphologic Characteristics of Intraperitoneally Injected Three-Dimensional-Cultured Tonsil-Derived Mesenchymal Stem Cells in a Murine Colitis Model Using Electron Microscopy"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-9693","authenticated-orcid":false,"given":"Ju Ran","family":"Byeon","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Mi","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang Hee","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Reum","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yehyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung Hyun","family":"Tae","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Mo","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye-Kyung","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki-Nam","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Ae","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ewha Medical Research Institute College of Medicine, Ewha Womans University , 260 Gonghangdae-ro, Gangseo\u2013gu, Seoul 07804 ,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"issue":"2","key":"2025092402280110800_ozae135-B1","doi-asserted-by":"publisher","first-page":"381","DOI":"10.3390\/pharmaceutics14020381","article-title":"Mesenchymal stem\/stromal cells and their paracrine activity-immunomodulation mechanisms and how to influence the therapeutic potential","volume":"14","author":"Alvites","year":"2022","journal-title":"Pharmaceutics"},{"issue":"4","key":"2025092402280110800_ozae135-B2","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s00109-013-1110-5","article-title":"Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model","volume":"92","author":"Bian","year":"2014","journal-title":"J Mol Med (Berl)"},{"issue":"1","key":"2025092402280110800_ozae135-B3","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1042\/bst20120192","article-title":"Role of stem-cell-derived microvesicles in the paracrine action of stem cells","volume":"41","author":"Camussi","year":"2013","journal-title":"Biochem Soc Trans"},{"issue":"5","key":"2025092402280110800_ozae135-B4","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1007\/s12015-021-10172-4","article-title":"Three-dimensional spheroid culture enhances multipotent differentiation and stemness capacities of human dental pulp-derived mesenchymal stem cells by modulating MAPK and NF-kB signaling pathways","volume":"17","author":"Chan","year":"2021","journal-title":"Stem Cell Rev Rep"},{"issue":"4","key":"2025092402280110800_ozae135-B5","doi-asserted-by":"publisher","first-page":"e1886","DOI":"10.1371\/journal.pone.0001886","article-title":"Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing","volume":"3","author":"Chen","year":"2008","journal-title":"PLoS One"},{"key":"2025092402280110800_ozae135-B6","doi-asserted-by":"publisher","first-page":"9636897221093312","DOI":"10.1177\/09636897221093312","article-title":"Newly generated 3D Schwann-like cell spheroids from human adipose-derived stem cells using a modified protocol","volume":"31","author":"Chen","year":"2022","journal-title":"Cell Transplant"},{"issue":"2","key":"2025092402280110800_ozae135-B7","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.cyto.2012.04.016","article-title":"Tonsil-derived mesenchymal progenitor cells acquire a follicular dendritic cell phenotype under cytokine stimulation","volume":"59","author":"Cho","year":"2012","journal-title":"Cytokine"},{"issue":"8","key":"2025092402280110800_ozae135-B8","doi-asserted-by":"publisher","first-page":"506","DOI":"10.4252\/wjsc.v11.i8.506","article-title":"Tonsil-derived stem cells as a new source of adult stem cells","volume":"11","author":"Cho","year":"2019","journal-title":"World J Stem Cells"},{"issue":"6","key":"2025092402280110800_ozae135-B9","doi-asserted-by":"publisher","first-page":"221","DOI":"10.3892\/ijmm.2021.5054","article-title":"Extracellular vesicles from tonsil-derived mesenchymal stromal cells show anti-tumor effect via miR-199a-3p","volume":"48","author":"Choi","year":"2021","journal-title":"Int J Mol Med"},{"issue":"6","key":"2025092402280110800_ozae135-B10","doi-asserted-by":"publisher","first-page":"e0225485","DOI":"10.1371\/journal.pone.0225485","article-title":"A comparative study of the capacity of mesenchymal stromal cell lines to form spheroids","volume":"15","author":"Deynoux","year":"2020","journal-title":"PLoS One"},{"issue":"11","key":"2025092402280110800_ozae135-B11","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.5966\/sctm.2015-0420","article-title":"Autophagy improves the immunosuppression of CD4+ T cells by mesenchymal stem cells through transforming growth factor-\u03b21","volume":"5","author":"Gao","year":"2016","journal-title":"Stem Cells Transl Med"},{"issue":"3","key":"2025092402280110800_ozae135-B12","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1053\/j.gastro.2008.11.041","article-title":"Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses","volume":"136","author":"Gonz\u00e1lez","year":"2009","journal-title":"Gastroenterology"},{"issue":"4","key":"2025092402280110800_ozae135-B13","doi-asserted-by":"publisher","first-page":"R83","DOI":"10.1186\/ar2459","article-title":"Human palatine tonsil: A new potential tissue source of multipotent mesenchymal progenitor cells","volume":"10","author":"Janjanin","year":"2008","journal-title":"Arthritis Res Ther"},{"issue":"4","key":"2025092402280110800_ozae135-B14","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1007\/s13770-017-0042-5","article-title":"Intracellular remodeling and accumulation of aberrant lysosomes in differentiation of tonsil-derived mesenchymal stem cells into parathyroid-like cells","volume":"14","author":"Jo","year":"2017","journal-title":"Tissue Eng Regen Med"},{"issue":"2","key":"2025092402280110800_ozae135-B15","doi-asserted-by":"publisher","first-page":"845","DOI":"10.21873\/invivo.12325","article-title":"Therapeutic effects of tonsil-derived mesenchymal stem cells in an atopic dermatitis mouse model","volume":"35","author":"Jung","year":"2021","journal-title":"In Vivo"},{"issue":"1","key":"2025092402280110800_ozae135-B16","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s13770-018-0160-8","article-title":"Conditioned medium from tonsil-derived mesenchymal stem cells relieves CCl(4)-induced liver fibrosis in mice","volume":"16","author":"Kim","year":"2019","journal-title":"Tissue Eng Regen Med"},{"issue":"12","key":"2025092402280110800_ozae135-B17","doi-asserted-by":"publisher","first-page":"e0225739","DOI":"10.1371\/journal.pone.0225739","article-title":"The efficacy of conditioned medium released by tonsil-derived mesenchymal stem cells in a chronic murine colitis model","volume":"14","author":"Lee","year":"2019","journal-title":"PLoS One"},{"key":"2025092402280110800_ozae135-B18","doi-asserted-by":"publisher","first-page":"9682757","DOI":"10.1155\/2016\/9682757","article-title":"How to improve the survival of transplanted mesenchymal stem cell in ischemic heart?","volume":"2016","author":"Li","year":"2016","journal-title":"Stem Cells Int"},{"issue":"6","key":"2025092402280110800_ozae135-B19","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1089\/scd.2012.0395","article-title":"Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis","volume":"22","author":"Li","year":"2013","journal-title":"Stem Cells Dev"},{"issue":"10","key":"2025092402280110800_ozae135-B20","doi-asserted-by":"publisher","first-page":"3499","DOI":"10.1182\/blood-2007-02-069716","article-title":"Immunomodulatory properties of mesenchymal stromal cells","volume":"110","author":"Nauta","year":"2007","journal-title":"Blood"},{"issue":"6","key":"2025092402280110800_ozae135-B21","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/scrt530","article-title":"Human mesenchymal stem cells\/multipotent stromal cells consume accumulated autophagosomes early in differentiation","volume":"5","author":"Nuschke","year":"2014","journal-title":"Stem Cell Res Ther"},{"issue":"4","key":"2025092402280110800_ozae135-B22","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1002\/stem.2575","article-title":"Concise review: MSC-derived exosomes for cell-free therapy","volume":"35","author":"Phinney","year":"2017","journal-title":"Stem Cells"},{"issue":"5-8","key":"2025092402280110800_ozae135-B23","doi-asserted-by":"publisher","first-page":"151041","DOI":"10.1016\/j.ejcb.2019.04.002","article-title":"Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives","volume":"98","author":"Regmi","year":"2019","journal-title":"Eur J Cell Biol"},{"issue":"1","key":"2025092402280110800_ozae135-B24","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s13287-019-1337-3","article-title":"Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN\/LPS-induced fulminant hepatic toxicity","volume":"10","author":"Regmi","year":"2019","journal-title":"Stem Cell Res Ther"},{"issue":"10","key":"2025092402280110800_ozae135-B25","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1080\/15548627.2020.1850608","article-title":"Enhanced viability and function of mesenchymal stromal cell spheroids is mediated via autophagy induction","volume":"17","author":"Regmi","year":"2021","journal-title":"Autophagy"},{"issue":"10","key":"2025092402280110800_ozae135-B26","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.3109\/14653249.2012.706708","article-title":"Tonsil-derived mesenchymal stromal cells: Evaluation of biologic, immunologic and genetic factors for successful banking","volume":"14","author":"Ryu","year":"2012","journal-title":"Cytotherapy"},{"issue":"1","key":"2025092402280110800_ozae135-B27","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1053\/j.gastro.2015.03.013","article-title":"Mesenchymal stem cells reduce colitis in mice via release of TSG6, independently of their localization to the intestine","volume":"149","author":"Sala","year":"2015","journal-title":"Gastroenterology"},{"issue":"12","key":"2025092402280110800_ozae135-B28","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3390\/biomedicines8120561","article-title":"TNF-\u03b1 Priming elicits robust immunomodulatory potential of human tonsil-derived mesenchymal stem cells to alleviate murine colitis","volume":"8","author":"Shin","year":"2020","journal-title":"Biomedicines"},{"issue":"1","key":"2025092402280110800_ozae135-B29","doi-asserted-by":"publisher","first-page":"19589","DOI":"10.1038\/s41598-021-98711-4","article-title":"Three-dimensional culture method enhances the therapeutic efficacies of tonsil-derived mesenchymal stem cells in murine chronic colitis model","volume":"11","author":"Song","year":"2021","journal-title":"Sci Rep"},{"issue":"2","key":"2025092402280110800_ozae135-B30","doi-asserted-by":"publisher","first-page":"119","DOI":"10.4166\/kjg.2017.69.2.119","article-title":"The therapeutic efficacy of tonsil-derived mesenchymal stem cells in dextran sulfate sodium-induced acute murine colitis model","volume":"69","author":"Song","year":"2017","journal-title":"Korean J Gastroenterol"},{"issue":"3","key":"2025092402280110800_ozae135-B31","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1002\/stem.302","article-title":"Reactive oxygen species inhibit adhesion of mesenchymal stem cells implanted into ischemic myocardium via interference of focal adhesion complex","volume":"28","author":"Song","year":"2010","journal-title":"Stem Cells"},{"issue":"7437","key":"2025092402280110800_ozae135-B32","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/nature11895","article-title":"FOXO3A directs a protective autophagy program in haematopoietic stem cells","volume":"494","author":"Warr","year":"2013","journal-title":"Nature"},{"issue":"5","key":"2025092402280110800_ozae135-B33","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1111\/joa.12229","article-title":"Characterization of long-term in vitro culture-related alterations of human tonsil-derived mesenchymal stem cells: Role for CCN1 in replicative senescence-associated increase in osteogenic differentiation","volume":"225","author":"Yu","year":"2014","journal-title":"J Anat"},{"issue":"8","key":"2025092402280110800_ozae135-B34","doi-asserted-by":"publisher","first-page":"e0183141","DOI":"10.1371\/journal.pone.0183141","article-title":"Therapeutic potential of tonsil-derived mesenchymal stem cells in dextran sulfate sodium-induced experimental murine colitis","volume":"12","author":"Yu","year":"2017","journal-title":"PLoS One"}],"container-title":["Microscopy and Microanalysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mam\/article-pdf\/31\/5\/ozae135\/64356961\/ozae135.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mam\/article-pdf\/31\/5\/ozae135\/64356961\/ozae135.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T06:28:10Z","timestamp":1758695290000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mam\/article\/doi\/10.1093\/mam\/ozae135\/8262645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,9,3]]}},"URL":"https:\/\/doi.org\/10.1093\/mam\/ozae135","relation":{},"ISSN":["1431-9276","1435-8115"],"issn-type":[{"value":"1431-9276","type":"print"},{"value":"1435-8115","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10]]},"published":{"date-parts":[[2025,9,3]]},"article-number":"ozae135"}}