Deutsch Intern
Musculoskeletal Center Wuerzburg

The extracellular matrix environment of bone marrow stromal cells


Ana Rita Pereira, Drenka Trivanovic, Bianca Schlierf, Theresa Kreuzahler, Marietta Herrmann
 

The extracellular matrix (ECM) microenvironment, namely its chemical composition and mechanical characteristics, is proven to distinctively modulate cell behavior and subsequently the full tissue dynamics. Despite the considerable volume of research into the biology and regenerative potential of mesenchymal stem/stromal cells (MSC), the lack of suitable models that recapitulate the in vivo cell-ECM interactions has led to poor clinical translation.

In the group, we develop unique human derived models based on decellularization techniques, e.g., 2D ECM-matrices and 3D scaffolds, in order to mimic the tissue-specific structure and composition of native bone. Likewise, we are able to replicate shear stress and compression forces, commonly sensed by bone cells in vivo, using an in-house developed automated bioreactor in collaboration with the chair for Tissue Engineering and Regenerative Medicine (TERM).
Experimentally, we validated the improved effect of dynamic conditions in scaffold repopulation and reported a stronger MSC integrin-mediated adhesion to the matrix with a boost of nascent ECM production.

Moreover, we aim to develop multimodal bone tissue models systems in both physiology and pathology conditions, in which specific experimental parameters can be systematically controlled. In several collaborative research projects, we establish bone-tumor models by studying simultaneously the chemical and physical properties of ECM and the healthy- cancerogenous cell interactions. With funding from the Max-Buchner-Forschungsstiftung, we further expand our dynamic 3D culture to also recapitulate the physiological low oxygen tension.


Publications

  • Ana Rita Pereira, Andreas Lipphaus, Mert Ergin, Sahar Salehi, Dominic Gehweiler, Maximilian Rudert, Jan Hansmann and Marietta Herrmann, Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell–Extracellular Matrix Interactions, Materials 2021, 14(16), 4431 doi.org/10.3390/ma14164431
  • Gloria Belén Ramírez-Rodríguez, Ana R. Pereira, Marietta Herrmann, Jan Hansmann, José M. Delgado-López, Simone Sprio, Anna Tampieri, Monica Sandri, Biomimetic mineralization promotes viability and differentiation of human mesenchymal stem cells in a perfusion bioreactor, International Journal of Molecular Sciences, 2021, 22(3):1447 doi.org/10.3390/ijms22031447
  • Ana Rita Pereira, Maximilian Rudert, Marietta Herrmann. Decellularized human bone as a 3D model to study skeletal progenitor cells in a natural environment. Methods Cell Biol. 2020;157:123-141. Epub 2019 Dec 31. doi: 10.1016/bs.mcb.2019.11.018
  • Ana Rita Pereira, Drenka Trivanovic, Marietta Herrmann. Approaches to mimic the complexity of the skeletal mesenchymal stem/stromal cell niche in vitro. European Cells & Materials. 2019 doi.org/10.22203/eCM.v037a07