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, 2009; Hellingman et?al., 2010; Pelttari et?al., 2006). A major challenge therefore is to identify the factors that support MSC expansion while maintaining their chondrogenic capacity, and additionally the factors that regulate hypertrophic maturation. To identify such factors, we took inspiration from the process of Selleckchem MK-2206 cartilage and bone formation during embryonic development. In developing mouse limbs, skeletal tissues are generated by a rapidly expanding population of multipotent mesenchymal cells, found at the tip of the embryonic limb bud (Rabinowitz and Vokes, 2012; Zeller et?al., 2009). The expansion of these multipotent cells is driven by the combination of WNT and FGF signals, secreted by the apical ectodermal ridge (ten Berge et?al., 2008a). The combination of WNT and FGF proteins synergistically supports the expansion of these cells in?vitro while maintaining their multilineage potential (Cooper et?al., 2011; ten Berge et?al., 2008a). Furthermore, WNT signals also play an important role during cell differentiation, where their ability to modulate chondrogenesis and induce osteogenesis is well established both in?vitro (Churchman et?al., 2012; Dong et?al., 2007; Jullien et?al., 2012) and in?vivo (Day et?al., 2005; Quarto et?al., 2010a, 2010b). In this paper, we show that the combination of WNT3A and FGF2 supports extensive expansion of adult human bone marrow-derived MSCs over multiple passages while maintaining robust chondrogenic potential. Furthermore, we show that inhibition of WNT signals during chondrogenic TRIB1 differentiation prevents undesired hypertrophic maturation, allowing the formation of stable cartilage in?vivo. Results WNT3A and FGF2 Synergistically Promote MSC Proliferation and Chondrogenic Potential MSCs were isolated from adult human bone marrow aspirates by selective plastic adherence (Figure?1A), followed by phenotypic characterization using flow cytometry. This confirmed the cells were positive (>95%) for the MSC markers CD73, CD90, and CD105 and negative www.selleckchem.com/products/pci-32765.html (