{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:06:12Z","timestamp":1790262372780,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,2,27]],"date-time":"2018-02-27T00:00:00Z","timestamp":1519689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"CancerFree Kids Foundation"},{"name":"Families for a Cure Foundation"},{"DOI":"10.13039\/100007520","name":"Nationwide Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007520","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is the delivery of anti-tumor therapeutic agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely used to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune diseases, and cancer. The pro-inflammatory cytokine interferon-gamma (IFN\u03b3) has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME). Despite this, clinical trials of systemic IFN\u03b3 therapy have failed due to the high blood concentration required and associated systemic toxicities. Here, we developed an intra-adrenal model of neuroblastoma, characterized by liver and lung metastases. We then engineered MSCs to deliver IFN\u03b3 directly to the TME. In vitro, these MSCs polarized murine macrophages to the M1 phenotype. In vivo, we attained a therapeutically active TME concentration of IFN\u03b3 without increased systemic concentration or toxicity. The TME-specific IFN\u03b3 reduced tumor growth rate and increased survival in two models of T cell deficient athymic nude mice. Absence of this benefit in NOD SCID gamma (NSG) immunodeficient mouse model indicates a mechanism dependent on the innate immune system. IL-17 and IL-23p19, both uniquely M1 polarization markers, transiently increased in the tumor interstitial fluid. Finally, the MSC vehicle did not promote tumor growth. These findings reveal that MSCs can deliver effective cytokine therapy directly to the tumor while avoiding systemic toxicity. This method transiently induces inflammatory M1 macrophage polarization, which reduces tumor burden in our novel neuroblastoma murine model.<\/jats:p>","DOI":"10.1002\/stem.2801","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T03:52:43Z","timestamp":1518407563000},"page":"915-924","source":"Crossref","is-referenced-by-count":67,"title":["Intratumoral Delivery of Interferon\u03b3-Secreting Mesenchymal Stromal Cells Repolarizes Tumor-Associated Macrophages and Suppresses Neuroblastoma Proliferation In Vivo"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-3663","authenticated-orcid":false,"given":"Theresa","family":"Relation","sequence":"first","affiliation":[{"name":"The Ohio State University Medical Scientist Training Program, Columbus, Ohio, USA"},{"name":"Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai","family":"Yi","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J.","family":"Guess","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"La Perle","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Otsuru","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suheyla","family":"Hasgur","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Dominici","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences of Children and Adults, University of Modena and Reggio Emilia, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Breuer","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin M.","family":"Horwitz","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer and Blood Diseases, The Research 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