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Cell Dev. Biol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Articular cartilage of the knee joint is avascular, exists under a low oxygen tension microenvironment, and does not self-heal when injured. Human infrapatellar fat pad-sourced mesenchymal stem cells (IFP-MSC) are an arthroscopically accessible source of mesenchymal stem cells (MSC) for the repair of articular cartilage defects. Human IFP-MSC exists physiologically under a low oxygen tension (i.e., 1\u20135%) microenvironment. Human bone marrow mesenchymal stem cells (BM-MSC) exist physiologically within a similar range of oxygen tension. A low oxygen tension of 2% spontaneously induced chondrogenesis in micromass pellets of human BM-MSC. However, this is yet to be demonstrated in human IFP-MSC or other adipose tissue-sourced MSC. In this study, we explored the potential of low oxygen tension at 2% to drive the <jats:italic>in vitro<\/jats:italic> chondrogenesis of IFP-MSC. We hypothesized that 2% O<jats:sub>2<\/jats:sub> will induce stable chondrogenesis in human IFP-MSC without the risk of undergoing endochondral ossification at ectopic sites of implantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Micromass pellets of human IFP-MSC were cultured under 2% O<jats:sub>2<\/jats:sub> or 21% O<jats:sub>2<\/jats:sub> (normal atmosphere O<jats:sub>2<\/jats:sub>) in the presence or absence of chondrogenic medium with transforming growth factor-\u03b23 (TGF\u03b23) for 3 weeks. Following <jats:italic>in vitro<\/jats:italic> chondrogenesis, the resulting pellets were implanted in immunodeficient athymic nude mice for 3 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A low oxygen tension of 2% was unable to induce chondrogenesis in human IFP-MSC. In contrast, chondrogenic medium with TGF\u03b23 induced <jats:italic>in vitro<\/jats:italic> chondrogenesis. All pellets were devoid of any evidence of undergoing endochondral ossification after subcutaneous implantation in athymic mice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcell.2021.703038","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T08:41:23Z","timestamp":1627288883000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Inability of Low Oxygen Tension to Induce Chondrogenesis in Human Infrapatellar Fat Pad Mesenchymal Stem Cells"],"prefix":"10.3389","volume":"9","author":[{"given":"Samia","family":"Rahman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander R. 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