Towards Inducing hMSC Chondrogenesis in Hydrogels through Treatment with Kartogenin

Osteoarthritis, a disease involving degradation of joints, affects over 70% of Americans over the age of 55. Current treatments are limited to pain management and surgery, neither of which restore the lost cartilage. Stem cells, a multipotent cell source, have the potential to restore lost cartilage, thus improving function while also alleviating symptoms.

            Kartogenin, a small, hydrophobic molecule discovered in 2012, has been shown to induce chondrogenesis in bone-marrow derived human mesenchymal stem cells (hMSCs). Kartogenin works by activating a variety of signaling pathways, including the TGF-β1 signaling pathway.  We hypothesize that cyclodextrins can be used to increase the solubility of kartogenin, allowing it to be readily incorporated into injectable hydrogel scaffolds for stem cell delivery and differentiation. We are currently treating hMSCs in micromass culture with kartogenin. We are assessing chondrogenesis by using alcian blue to stain glycosaminoglycans, which are part of the extracellular matrix of chondrocytes.

            We are also examining the encapsulation of kartogenin within cyclodextrins and the release of kartogenin from cyclodextrins. Following this work, we will treat micromass cultures with kartogenin-containing cyclodextrins and examine chondrogenesis through alcian blue staining and immunohistochemistry for collagen II. Future work will examine the release of kartogenin from cyclodextrins when encapsulated within gellan hydrogels with and without hMSCs..