{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:02:03Z","timestamp":1777510923977,"version":"3.51.4"},"reference-count":28,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:p>Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6 concentration in the supernatant was measured using ELISA. The correlation between the anti-inflammatory effect of hUCMSCs and IL-6 levels and the relevant roles of IL-6 and IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was further evaluated. We reported that hUCMSCs did not initially exert any inhibitory effect on PHA-stimulated proliferation; however, a potent inhibitory effect on PHA-stimulated proliferation was observed, and the IL-6 concentration reached approximately 1000 ng\/mL after 72 hours. Exogenous 1000 ng\/mL IL-6 inhibited PHA-stimulated inflammation but less so than hUCMSCs. The inhibitory effects of hUCMSCs on PHA-stimulated PBMCs disappeared after adding an IL-6 neutralizing antibody or pretreatment with tocilizumab (TCZ), an IL-6R antagonist. hUCMSCs exert excellent anti-inflammatory effects by inducing higher IL-6 levels, which is different from TCZ. High concentration of IL-6 cytokine secretion plays an important role in the anti-inflammatory effect of hUCMSC therapy. Initial hUCMSC therapy, followed by TCZ, seems to optimize the therapeutic potential to treat COVID-19-related acute respiratory distress syndrome (ARDS).<\/jats:p>","DOI":"10.1177\/09636897211054481","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T15:11:50Z","timestamp":1636557110000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["High Induction of IL-6 Secretion From hUCMSCs Optimize the Potential of hUCMSCs and TCZ as Therapy for COVID-19-Related ARDS"],"prefix":"10.1177","volume":"30","author":[{"given":"Huei-Yu","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"},{"name":"Department of Chemistry, Chung Yuan Christian University, Taoyuan"},{"name":"Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-Ping","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"},{"name":"Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Long","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuo-Ting","family":"Chang","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Lung","family":"Chang","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"},{"name":"Department of Urology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"},{"name":"Department of Urology, School of Medicine, National Yang-Ming University, Taipei"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Hsun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Jen","family":"Chang","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"},{"name":"Department of Food Science, Fu Jen Catholic University, New Taipei City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Hua","family":"Chiu","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yui Whei","family":"Chen-Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chung Yuan Christian University, Taoyuan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4117-4379","authenticated-orcid":false,"given":"Chin-Kan","family":"Chan","sequence":"additional","affiliation":[{"name":"Translational Medicine Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"},{"name":"Department of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan"},{"name":"Department of Biotechnology, Ming Chuan University, Taoyuan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"bibr1-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25770"},{"key":"bibr2-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.01.009"},{"key":"bibr3-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25948"},{"key":"bibr4-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102568"},{"key":"bibr5-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.03.300"},{"key":"bibr6-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000026023"},{"key":"bibr7-09636897211054481","doi-asserted-by":"publisher","DOI":"10.2217\/fvl-2020-0410"},{"key":"bibr8-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02165-4"},{"key":"bibr9-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1080\/17476348.2021.1848555"},{"issue":"1","key":"bibr10-09636897211054481","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13063-020-04964-1","volume":"22","author":"Payares-Herrera C","year":"2021","journal-title":"Trials"},{"key":"bibr11-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1016\/j.pulmoe.2020.07.003"},{"key":"bibr12-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1177\/09636897211021008"},{"key":"bibr13-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.07.011"},{"key":"bibr14-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31825940a4"},{"key":"bibr15-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kex513"},{"key":"bibr16-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.04.014"},{"key":"bibr17-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a123261"},{"key":"bibr18-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.11.5.613"},{"key":"bibr19-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2017.06.008"},{"key":"bibr20-09636897211054481","doi-asserted-by":"publisher","DOI":"10.2174\/156652412800619950"},{"key":"bibr21-09636897211054481","doi-asserted-by":"publisher","DOI":"10.2174\/1574888X11308020005"},{"key":"bibr22-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-016-0961-y"},{"key":"bibr23-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e31821aba18"},{"key":"bibr24-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41910-x"},{"key":"bibr25-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-014-0042-4"},{"key":"bibr26-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7276"},{"key":"bibr27-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2006-0548"},{"key":"bibr28-09636897211054481","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2005.11.003"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09636897211054481","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09636897211054481","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09636897211054481","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:38:52Z","timestamp":1777390732000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09636897211054481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,1]]},"references-count":28,"alternative-id":["10.1177\/09636897211054481"],"URL":"https:\/\/doi.org\/10.1177\/09636897211054481","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,1]]},"article-number":"09636897211054481"}}