{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:57:59Z","timestamp":1780099079338,"version":"3.54.0"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Masquelet's induced membrane technique (MIMT) is a staged surgical procedure that leverages the foreign body induced membrane (IM) that forms around a cement spacer placed into a segmental bone defect to support subsequent bone grafting. The mechanisms by which the IM supports bone consolidation are not fully understood. We present an indirect coculture system for studying IM\u2010MSC interactions using a rat model of MIMT. Compared to control cells, MSC <jats:italic>Tnap<\/jats:italic> (alkaline phosphatase) was induced by 4\u2010 but not 8\u2010week IM. MSC <jats:italic>Spp1<\/jats:italic> (Osteopontin) was attenuated by both 4\u2010 and 8\u2010week IM. Although <jats:italic>Tnfrsf11b<\/jats:italic> (osteoprotegrin) in MSC exposed to IM was not different from control cells, it was induced by 8\u2010week IM compared to 4\u2010week IM. MSC <jats:italic>Tnfsf11<\/jats:italic> (RANKL) was reduced by 4\u2010week and 8\u2010week IM. MSC <jats:italic>Thbs2<\/jats:italic> (Tsp2) was induced by 8\u2010week but not 4\u2010week IM. Ablation of macrophages in IM blocked the induction of <jats:italic>Thbs2<\/jats:italic> by 8\u2010week IM. MSC Col1a1 expression was not affected under any condition tested. TMT proteomics analysis of IM\u2010conditioned medium revealed 150 unique secreted proteins, 7 of which were differentially abundant (fold change\u2009\u2265\u20092 and FDR corrected <jats:italic>p<\/jats:italic>\u2009\u2264\u20090.05) in 8\u2010week versus 4\u2010week IM secretomes. All differentially abundant proteins were elevated in medium conditioned by 8\u2010week IM. Our data suggest that factor(s) secreted by IM resident cells affect MSC gene expression, and that duration of IM development influences the potency and nature of this paracrine effect. Patient\u2010specific factors including age and interval between MIMT surgeries may affect IM biological potency and graft to bone consolidation.<\/jats:p>","DOI":"10.1002\/jor.26053","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:34:50Z","timestamp":1739270090000},"page":"922-930","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Paracrine Influence of Masquelet's Induced Membrane on Marrow Derived Mesenchymal Stem Cells"],"prefix":"10.1002","volume":"43","author":[{"given":"Meredyth","family":"Bowman","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery University of Michigan School of Medicine, A. 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