@article{HanetsederLevstekTeuschlWolleretal., author = {Hanetseder, Dominik and Levstek, Tina and Teuschl-Woller, Andreas and Frank, Julia Katharina and Schaedl, Barbara and Redl, Heinz and Marolt Presen, Darja}, title = {Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age}, series = {Front Bioeng Biotechnol}, volume = {11}, journal = {Front Bioeng Biotechnol}, doi = {https://doi.org/10.3389/fbioe.2023.1214019}, abstract = {Regeneration of bone defects is often limited due to compromised bone tissue physiology. Previous studies suggest that engineered extracellular matrices enhance the regenerative capacity of mesenchymal stromal cells. In this study, we used human-induced pluripotent stem cells, a scalable source of young mesenchymal progenitors (hiPSC-MPs), to generate extracellular matrix (iECM) and test its effects on the osteogenic capacity of human bone-marrow mesenchymal stromal cells (BMSCs). iECM was deposited as a layer on cell culture dishes and into three-dimensional (3D) silk-based spongy scaffolds. After decellularization, iECM maintained inherent structural proteins including collagens, fibronectin and laminin, and contained minimal residual DNA. Young adult and aged BMSCs cultured on the iECM layer in osteogenic medium exhibited a significant increase in proliferation, osteogenic marker expression, and mineralization as compared to tissue culture plastic. With BMSCs from aged donors, matrix mineralization was only detected when cultured on iECM, but not on tissue culture plastic. When cultured in 3D iECM/silk scaffolds, BMSCs exhibited significantly increased osteogenic gene expression levels and bone matrix deposition. iECM layer showed a similar enhancement of aged BMSC proliferation, osteogenic gene expression, and mineralization compared with extracellular matrix layers derived from young adult or aged BMSCs. However, iECM increased osteogenic differentiation and decreased adipocyte formation compared with single protein substrates including collagen and fibronectin. Together, our data suggest that the microenvironment comprised of iECM can enhance the osteogenic activity of BMSCs, providing a bioactive and scalable biomaterial strategy for enhancing bone regeneration in patients with delayed or failed bone healing.}, subject = {aging}, language = {en} } @article{GollmannTepekoeylueGraberHirschetal., author = {Gollmann-Tepek{\"o}yl{\"u}, Can and Graber, Michael and Hirsch, Jakob and Mair, Sophia and Naschberger, Andreas and P{\"o}lzl, Leo and N{\"a}gele, Felix and Kirchmair, Elke and Degenhart, Gerald and Demetz, Egon and Hilbe, Richard and Chen, Hao-Yu and Engert, James C and B{\"o}hm, Anna and Franz, Nadja and Lobenwein, Daniela and Lener, Daniela and Fuchs, Christiane and Weihs, Anna and T{\"o}chterle, Sonja and Vogel, Georg F and Schweiger, Victor and Eder, Jonas and Pietschmann, Peter and Seifert, Markus and Kronenberg, Florian and Coassin, Stefan and Blumer, Michael and Hackl, Hubert and Meyer, Dirk and Feuchtner, Gudrun and Kirchmair, Rudolf and Troppmair, Jakob and Krane, Markus and Weiss, G{\"u}nther and Tsimikas, Sotirios and Thanassoulis, George and Grimm, Michael and Rupp, Bernhard and Huber, Lukas A and Zhang, Shen-Ying and Casanova, Jean-Laurent and Tancevski, Ivan and Holfeld, Johannes}, title = {Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification}, series = {Circulation}, volume = {147}, journal = {Circulation}, number = {20}, doi = {10.1161/CIRCULATIONAHA.122.063481}, pages = {1518 -- 1533}, subject = {Toll-like receptor 3}, language = {en} }