TY  - JOUR
A1  - Hanetseder, Dominik
A1  - Levstek, Tina
A1  - Teuschl-Woller, Andreas
A1  - Frank, Julia Katharina
A1  - Schaedl, Barbara
A1  - Redl, Heinz
A1  - Marolt Presen, Darja
T1  - Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age
JF  - Front Bioeng Biotechnol
N2  - 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.
KW  - aging
KW  - iPSCs
KW  - osteogenic differentiation
KW  - bone marrow stromal cells
KW  - extracellular matrix
Y1  - 
U6  - http://dx.doi.org/https://doi.org/10.3389/fbioe.2023.1214019
VL  - 11
ER  - 
TY  - JOUR
A1  - Gollmann-Tepeköylü, Can
A1  - Graber, Michael
A1  - Hirsch, Jakob
A1  - Mair, Sophia
A1  - Naschberger, Andreas
A1  - Pölzl, Leo
A1  - Nägele, Felix
A1  - Kirchmair, Elke
A1  - Degenhart, Gerald
A1  - Demetz, Egon
A1  - Hilbe, Richard
A1  - Chen, Hao-Yu
A1  - Engert, James C
A1  - Böhm, Anna
A1  - Franz, Nadja
A1  - Lobenwein, Daniela
A1  - Lener, Daniela
A1  - Fuchs, Christiane
A1  - Weihs, Anna
A1  - Töchterle, Sonja
A1  - Vogel, Georg F
A1  - Schweiger, Victor
A1  - Eder, Jonas
A1  - Pietschmann, Peter
A1  - Seifert, Markus
A1  - Kronenberg, Florian
A1  - Coassin, Stefan
A1  - Blumer, Michael
A1  - Hackl, Hubert
A1  - Meyer, Dirk
A1  - Feuchtner, Gudrun
A1  - Kirchmair, Rudolf
A1  - Troppmair, Jakob
A1  - Krane, Markus
A1  - Weiss, Günther
A1  - Tsimikas, Sotirios
A1  - Thanassoulis, George
A1  - Grimm, Michael
A1  - Rupp, Bernhard
A1  - Huber, Lukas A
A1  - Zhang, Shen-Ying
A1  - Casanova, Jean-Laurent
A1  - Tancevski, Ivan
A1  - Holfeld, Johannes
T1  - Toll-Like Receptor 3 Mediates Aortic Stenosis Through a Conserved Mechanism of Calcification
JF  - Circulation
KW  - Toll-like receptor 3
KW  - aortic valve disease
KW  - biglycan
KW  - extracellular matrix
KW  - osteogenesis
Y1  - 
U6  - http://dx.doi.org/10.1161/CIRCULATIONAHA.122.063481
VL  - 147
IS  - 20
SP  - 1518
EP  - 1533
ER  -