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Here we used a hanging drop protocol to prepare human MSCs (hMSCs) as spheroids that maximally expressed TNF\u03b1 stimulated gene\/protein 6 (TSG-6), the antiinflammatory protein that was expressed at high levels by hMSCs trapped in the lung after i.v. infusion and that largely explained the beneficial effects of hMSCs in mice with myocardial infarcts. The properties of spheroid hMSCs were found to depend critically on the culture conditions. Under optimal conditions for expression of TSG-6, the hMSCs also expressed high levels of stanniocalcin-1, a protein with both antiinflammatory and antiapoptotic properties. In addition, they expressed high levels of three anticancer proteins: IL-24, TNF\u03b1-related apoptosis inducing ligand, and CD82. The spheroid hMSCs were more effective than hMSCs from adherent monolayer cultures in suppressing inflammatory responses in a coculture system with LPS-activated macrophages and in a mouse model for peritonitis. In addition, the spheroid hMSCs were about one-fourth the volume of hMSCs from adherent cultures. Apparently as a result, larger numbers of the cells trafficked through the lung after i.v. infusion and were recovered in spleen, liver, kidney, and heart. The data suggest that spheroid hMSCs may be more effective than hMSCs from adherent cultures in therapies for diseases characterized by sterile tissue injury and unresolved inflammation and for some cancers that are sensitive to antiinflammatory agents.<\/jats:p>","DOI":"10.1073\/pnas.1008117107","type":"journal-article","created":{"date-parts":[[2010,7,20]],"date-time":"2010-07-20T00:50:30Z","timestamp":1279587030000},"page":"13724-13729","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":895,"title":["Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties"],"prefix":"10.1073","volume":"107","author":[{"given":"Thomas J.","family":"Bartosh","sequence":"first","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joni H.","family":"Yl\u00f6stalo","sequence":"additional","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arezoo","family":"Mohammadipoor","sequence":"additional","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Bazhanov","sequence":"additional","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Coble","sequence":"additional","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent","family":"Claypool","sequence":"additional","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryang Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hosoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darwin J.","family":"Prockop","sequence":"additional","affiliation":[{"name":"Texas A&amp;M Health Science Center, College of Medicine, Institute for Regenerative Medicine at Scott &amp; White, Temple, TX 76502"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,7,19]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"267","article-title":"Fibroblast precursors in normal and irradiated mouse hematopoietic organs","volume":"4","author":"Friedenstein AJ","year":"1976","unstructured":"AJ Friedenstein, JF Gorskaja, NN Kulagina, Fibroblast precursors in normal and irradiated mouse hematopoietic organs. 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