{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:44:20Z","timestamp":1790228660830,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Trizell GmbH"},{"name":"German Research Society"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DA572\/11-4"],"award-info":[{"award-number":["DA572\/11-4"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DA572\/11\u20104"],"award-info":[{"award-number":["DA572\/11\u20104"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mesenchymal stem cells (MSCs) are used in various clinical and preclinical models for immunomodulation. However, it remains unclear how the immunomodulatory effect of MSC is communicated. MSC-induced immunomodulation is known to be mediated through both MSC-secreted cytokines and direct cell-cell interactions. Recently, it has been demonstrated that metabolically inactive, heat-inactivated MSCs (HI-MSCs) have similar anti-inflammatory capacities in LPS-induced sepsis compared with viable MSC. To further investigate the immunomodulatory effects of MSC, we introduced MSC and HI-MSC in two animal models with different immunological causes. In the first model, allogeneic hearts were transplanted from C57BL\/6 mice to BALB\/c recipients. MSC in combination with mycophenolate mofetil (MMF) significantly improved graft survival compared with MMF alone, whereas the application of HI-MSC had no effect on graft survival. We revealed that control MSC dose-dependently inhibited CD3+ and CD8+ T-cell proliferation in vitro, whereas HI-MSC had no effect. In the second model, sepsis was induced in mice via cecal ligation and puncture. HI-MSC treatment significantly improved the overall survival, whereas control MSCs had no effect. in vitro studies demonstrated that HI-MSCs are more effectively phagocytosed by monocytes than control MSCs and induced cell death in particular of activated CD16+ monocytes, which may explain the immune protective effect of HI-MSC in the sepsis model. The results of our study demonstrate that MSC-mediated immunomodulation in sepsis is dependent on a passive recognition of MSC by monocytes, whereas fully functional MSCs are required for inhibition of T-cell-mediated allograft rejection.<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n               <\/jats:sec>","DOI":"10.1002\/stem.3165","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T13:43:31Z","timestamp":1582724611000},"page":"797-807","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Differential effects of heat-inactivated, secretome-deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1257-5517","authenticated-orcid":false,"given":"Andreas R. R.","family":"Weiss","sequence":"first","affiliation":[{"name":"1 Department of Surgery and Experimental Surgery, University Medical Center, Regensburg, Germany"},{"name":"2 Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin, St. James' Hospital, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Lee","sequence":"additional","affiliation":[{"name":"3 Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands"},{"name":"4 Biomedical Sciences, University of Guelph, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Eggenhofer","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and Experimental Surgery, University Medical Center, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Geissler","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and Experimental Surgery, University Medical Center, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander S.","family":"Korevaar","sequence":"additional","affiliation":[{"name":"3 Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yorick","family":"Soeder","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and Experimental Surgery, University Medical Center, Regensburg, Germany"},{"name":"5 Department of Surgery, Robert Bosch Health Campus, Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Schlitt","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and Experimental Surgery, University Medical Center, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward K.","family":"Geissler","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and Experimental Surgery, University Medical Center, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Hoogduijn","sequence":"additional","affiliation":[{"name":"3 Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc H.","family":"Dahlke","sequence":"additional","affiliation":[{"name":"1 Department of Surgery and Experimental Surgery, University Medical Center, Regensburg, Germany"},{"name":"5 Department of Surgery, Robert Bosch Health Campus, Stuttgart, 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