Melanie aims to understand the effects of physical, chemical and biological cues on human primary cells and progenitor cell fate to aid in the design of studies using these cells for tissue-specific therapeutic applications. As many variables strongly influence the phenotype and hence function of the cells, my group aims to compare progenitor cells derived from different tissue origins, effects of different culture systems (2D vs. 3D), scaffold types (e.g. different biomaterial effects), and choice of expansion conditions with an aim of producing GMP-compliant and clinically translational conditions.
Another major area that Melanie is focusing on is production of tools for sustained delivery of cells and therapeutic agents from microscale particles called microbeads and microspheres. These spherical three-dimensional (3D) microenvironments can be used for encapsulation and spatiotemporal controlled release of cells, concentrated growth factors, a drug of interest or inflammatory modulators.
Microbeads (e.g. 200-300 µm in diameter) act as a physiological matrix for the cells. Moreover, they can be completely broken down at a controlled rate through cell binding and secretion of matrix metalloproteinase enzymes produced by the cells themselves, allowing the cells to easily spread and interact with local cells.
Microspheres, which are smaller in size (e.g. 5-30 µm in diameter), can used to deliver growth factors or therapeutic agents. The release kinetics of such factors can be tailored for burst, short- or long-term release for in vitro or in vivo applications. Melanie uses naturally-derived biomaterials such as fibrin, collagen, alginate, gelatin and chitosan for tissue engineering applications as these natural polymers are degraded over time by the cells themselves. Because of their microscale size and naturally-derived biomaterial origin, microbeads and microspheres can be injected safely or delivered as a concentrated paste for therapeutic effects.
An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications. Khella CM, Asgarian R, Horvath JM, Rolauffs B, Hart ML. Int J Mol Sci. 2021 Feb 17;22:1996
Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function. Lauer JC, Selig M, Hart ML, Kurz B, Rolauffs B. Int J Mol Sci. 2021 Mar 23;22(6):3279
Shaping the cell and the future: recent advancements in biophysical aspects relevant to regenerative medicine. Hart ML, Lauer JC, Selig M, Hanak M, Walters B, Rolauffs B. Invited review. Journal of Functional Morphology and Kinesiology 2018, 3(1), 2
Engineering the geometrical shape of mesenchymal stromal cells through defined cyclic stretch regimens. Walters B, Uynuk-Ool T, Rothdiener M, Palm J, Hart ML, Stegemann JP, Rolauffs B. Scientific Reports, 2017, Jul 26;7(1):6640
Expression of desmoglein 2, desmocollin 3 and plakophilin 2 in placenta and bone marrow-derived mesenchymal stromal cells. Hart ML, Rusch E, Kaupp M, Nieselt K, Aicher WK. Stem Cell Reviews and Reports. 2017 Apr;13(2):258-266
The geometrical shape of mesenchymal stromal cells measured by quantitative shape descriptors is determined by the stiffness of the biomaterial and by cyclic tensile forces. Uynuk-Ool T, Rothdiener M, Walters B, Hegemann M, Palm J, Nguyen P, Seeger T, Stöckle U, Stegemann JP, Aicher WK, Kurz B, Hart ML, Klein G, Rolauffs B. J Tissue Eng Regen Med. 2017 Mar 29
Comparative phenotypic transcriptional characterization of human full-term placenta-derived mesenchymal stromal cells compared to bone marrow-derived mesenchymal stromal cells after differentiation in myogenic medium. Hart ML, Kaupp M, Brun J, Aicher WK. Placenta. 2017 Jan;49:64-67
Expression of CD146 on human placenta-derived mesenchymal stromal cells and their osteogenic differentiation capacity are modulated by factors contained in platelet lysate Verpoorten S, Abruzzese T, Pils A, Abele H, Hart ML, Aicher WK, J Regen Med. 2017 Jan, 6:1
Effect of matrix nanoscale elasticity on mesenchymal stem cell morphology and differentiation. Bachelor thesis. Woergoetter K.; supervisor, Hart ML. Inter-University Center for Medical Technologies Stuttgart – Eberhard Karls Universität Tübingen (IZST), 2016
Choice of xenogenic-free expansion media significantly influences the myogenic differentiation potential of human bone marrow-derived mesenchymal stromal cells. Brun J, Abruzzese T, Rolauffs B, Aicher WK, Hart ML. Cytotherapy. 2016 Mar;18(3):344-59
Bone marrow-derived mesenchymal stromal cells differ in their attachment to fibronectin-derived peptides from term placenta-derived mesenchymal stromal cells. Maerz, JK, Roncoroni LP, Goldeck D, Abruzzese T, Kalbacher H, Rolauffs B, DeZwart P, Nieselt K, Hart ML, Klein G, Aicher WK. Stem Cell Research & Therapy 2016 Feb 11;7:29
Generation of microspheres and microbeads to facilitate myogenic differentiation of mesenchymal stem cells. Bachelor thesis. Erweid P.; supervisor, Hart ML. Biotechnology, Hochschule Furtwangen, 2015
Generation of an in vitro three-dimensional environment for the modification of human mesenchymal stem cells using microspheres and microbeads. Bachelor thesis. Volkov E.; supervisor, Hart ML. Medical and Life Sciences, Hochschule Furtwangen, 2015
Development of novel biomaterials for modification of mesenchymal stromal stem cells in vivo Bachelor thesis. Zippusch S.; supervisor, Hart ML. Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Krems, 2015
Smooth muscle-like cells generated from human mesenchymal stromal cells display marker gene expression and electrophysiological competence comparable to bladder smooth muscle cells. Brun J, Lutz KA, Neumayer KMH, Klein G, Seeger T, Uynuk-Ool T, Wörgötter K, Schmid S, Kraushaar U, Guenther E, Rolauffs B, Aicher WK, Hart ML. PlosOne. 2015 Dec 16;10(12):e0145153
Human placenta-derived CD146-positive mesenchymal stromal cells display a distinct osteogenic differentiation potential. Ulrich C, Abruzzese T, Maerz JK, Ruh M, Amend B,Benz K, Rolauffs B, Harald A, Hart ML, Aicher WK. Stem Cells and Development. 2015. 24(13): 1558-1569
Low osteogenic differentiation potential of placenta-derived mesenchymal stromal cells correlates with low expression of the transcription factors runx2 and twist2. Ulrich C, Rolauffs B, Abele H, Bonin M, Nieselt K, Hart ML, Aicher WK. Stem Cells and Development. 2013. 22(21): 2859-2872
The TGF-β1-induced expression of matrix metalloproteinases in mesenchymal stromal cells is influenced by type of substrate. Warstat K, Felka T, Mittag F, Kluba T, Rolauffs B, Klein G, Hart ML, Aicher WK. Journal of Tissue Science & Engineering. 2011; 22:108