MAY 23, 2019 09:00 AM PDT

Doing More with Less: Stem Cells Regulate Their Fate by Altering Their Stiffness

  • Project Leader/Postdoctoral Associate, Biomedical Sciences and Regenerative Technologies, Institute for Macromolecular Chemistry, University of Freiburg, Germany.
      Dr. Melika Sarem is a Project Leader/Postdoc in the area of Biomedical Sciences and Regenerative Technologies in the Institute for Macromolecular Chemistry at the University of Freiburg, Germany. Melika received her Master's degree with honors in Biomedical Engineering, from Amirkabir University of Technology, Tehran, Iran. She then earned her Ph.D. with Summa Cum Laude in Natural Sciences from University of Freiburg in 2017 under supervision of Prof. V. Prasad Shastri specializing in biomimetic materials and stem cell biology. Her doctoral thesis "Role of Intrinsically Disordered Phosphoprotein Secondary Structure in Bone Biomineralization and Impact of Biomimetic Apatite on Endochondral Ossification" received The Best Doctoral Dissertation Award (Arthur-Lüttringhaus-Preis-2018) from University of Freiburg. In her doctoral effort Melika developed biomimetic system to engineer bone-like hydroxyapatite and using this system, she investigated how bone mineral phase impacts human bone marrow derived mesenchymal stem cells (MSCs) fate. She discovered bone mineral phase stimulates extracellular calcium sensing receptor (CaSR) in MSCs, and the hyperstimulation of this receptor blocks endochondral ossification and strictly promotes formation of bone via intramembranous ossification in MSCs.
      Currently, Melika works on several multidisciplinary projects at the intersection of biophysics, materials science and developmental biology with a translational focus that incorporates various cutting edge technologies such as 3D bioprinting.
      Melika's research has resulted in several publications in highly prestigious journals including Advanced Materials, Proceedings of the National Academy of Sciences - USA (PNAS) and Small, which has been extensively covered by the press. Her research impact in orthopedic tissue engineering and regenerative medicine has also been recently recognized by orthoregeneration network (ON) via ON/EORS education scholarship.

    DATE:  May 23, 2019
    TIME:   9:00am PDT, 12:00pm EDT
    Although mesenchymal stem/stromal cells (MSCs) chondrogenic differentiation has been thoroughly investigated, the rudiments for enhancing chondrogenesis have remained largely dependent on external cues. Since aggregation of MSCs, a prerequisite for chondrogenesis, generates tension within the cell agglomerate, we theorized that the initial number of the cells within the aggregate could function as an intrinsic activator of a mechanobiology paradigm and alter the outcomes. We discovered that reducing aggregate cell number (ACN) from 500k to 70k leads to activation and acceleration of the chondrogenic differentiation, independent of soluble chondro-inductive factors, via β-catenin dependent TCF/LEF transcriptional activity and expression of anti-apoptotic protein survivin. Our state-of-the-art mechanical testing revealed a correlation between progression of chondrogenesis and emergence of stiffer cell phenotype. In-depth Affymetrix gene array analysis proposed that the down-regulation of genes associated with lipid synthesis and regulation could account for observed outcomes. Furthermore, we illustrate that implanting aggregates within collagenous matrix not only decreases the necessity for high quantity of cells but also leads to drastic improvement in quality of the deposited tissue. In summary, our study presents a simple and donor-independent strategy to enhance the efficiency of MSCs chondrogenic differentiation and demonstrates a correlation between MSCs chondrogenesis and mechanical properties with potential translational applications.
    Learning Objectives:
    • Role of biophysics in mesenchymal stem cell biology
    • Mechanosensing proteins in chondrogenic differentiation
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