{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:54:41Z","timestamp":1791287681434,"version":"4.1.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Institutes of Health Intramural Research Program"},{"name":"Radiation\/Nuclear Medical Countermeasures Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Exposure to ionizing radiation (IR) can result in the development of cutaneous fibrosis, for which few therapeutic options exist. We tested the hypothesis that bone marrow-derived mesenchymal stem cells (BMSC) would favorably alter the progression of IR-induced fibrosis. We found that a systemic infusion of BMSC from syngeneic or allogeneic donors reduced skin contracture, thickening, and collagen deposition in a murine model. Transcriptional profiling with a fibrosis-targeted assay demonstrated increased expression of interleukin-10 (IL-10) and decreased expression of IL-1\u03b2 in the irradiated skin of mice 14 days after receiving BMSC. Similarly, immunoassay studies demonstrated durable alteration of these and several additional inflammatory mediators. Immunohistochemical studies revealed a reduction in infiltration of proinflammatory classically activated CD80+ macrophages and increased numbers of anti-inflammatory regulatory CD163+ macrophages in irradiated skin of BMSC-treated mice. In vitro coculture experiments confirmed that BMSC induce expression of IL-10 by activated macrophages, suggesting polarization toward a regulatory phenotype. Furthermore, we demonstrated that tumor necrosis factor-receptor 2 (TNF-R2) mediates IL-10 production and transition toward a regulatory phenotype during coculture with BMSC. Taken together, these data demonstrate that systemic infusion of BMSC can durably alter the progression of radiation-induced fibrosis by altering macrophage phenotype and suppressing local inflammation in a TNF-R2-dependent fashion.<\/jats:p>","DOI":"10.1002\/stem.1483","type":"journal-article","created":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T20:21:14Z","timestamp":1375129274000},"page":"2231-2241","source":"Crossref","is-referenced-by-count":110,"title":["Mesenchymal stem cells inhibit cutaneous radiation-induced fibrosis by suppressing chronic inflammation"],"prefix":"10.1093","volume":"31","author":[{"given":"Jason A.","family":"Horton","sequence":"first","affiliation":[{"name":"Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn E.","family":"Hudak","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Joo","family":"Chung","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayla O.","family":"White","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley T.","family":"Scroggins","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey F.","family":"Burkeen","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah E.","family":"Citrin","sequence":"additional","affiliation":[{"name":"Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,10,28]]},"reference":[{"key":"2022011118415342500_stem1483-bib-0001","doi-asserted-by":"crossref","first-page":"130","DOI":"10.2174\/092986709787002790","article-title":"Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: Therapeutic implications","volume":"16","author":"Zhao","year":"2009","journal-title":"Curr Med Chem"},{"key":"2022011118415342500_stem1483-bib-0002","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0360-3016(01)02732-8","article-title":"Altered proliferation and differentiation of human epidermis in cases of skin fibrosis after radiotherapy","volume":"53","author":"Sivan","year":"2002","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2022011118415342500_stem1483-bib-0003","doi-asserted-by":"crossref","first-page":"e29399","DOI":"10.1371\/journal.pone.0029399","article-title":"Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring","volume":"6","author":"Gallet","year":"2011","journal-title":"PLoS One"},{"key":"2022011118415342500_stem1483-bib-0004","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. 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