Properties of mesenchymal stromal/stem cells.
On the left the central in vitro cultured stem cell with its characteristic fibroblast (plastic adherent) morphology is depicted. In addition, these cells are characterized by a particular pattern of surface antigens (“immune phenotype”), the secretion of soluble factors (“paracrine effects”) and their differentiation (“differentiation”) into distinct mesenchymal cell lineages. For more information see text.
In this research topic a concrete translation of results from our own basic research into a medical approach is followed with the DFG-funded research unit FOR 2180: Together with colleagues from the LUH and the Technical University Braunschweig we are working in NIFE on the development of a novel biodegradable and graded implant with the aim of restoring tendon-bone junctions in vivo. By identification of novel factors we aim to avoid cell-based therapies with the ultimate aim of optimized treatment for patients.
Optimization of neuroprostheses
Function of human MSCs
a) Maintenance of stem cell functions
b) Generation of cells of the musculo-skeletal system
under normal and inflammatory conditions (e. g. rheumatoid arthritis)
Development of optimized methods for isolation, cultivation and clinical use of MSCs
Using biochemical, molecular-biological and cell-biological methods we aim to enhance the understanding of basic principles of stem cell functions under normal and inflammatory conditions. The factors that we investigate contribute to either the maintenance and so-called potency of stem cells or control the differentiation of the stem cells into distinct cell types. This differentiation can be altered under inflammatory conditions. “Factors” in the narrower sense are genes or proteins like growth and transcription factors including Bone Morphogenetic Protein 2 (BMP2) or Smad8 L+MH2, cell-surface antigens or signaling mediator proteins like Transforming Growth Factor-Beta Activated Kinase 1 (TAK1) that guide cellular processes. “Factors” in the wider sense may also comprise native or genetically modified stem cells and other cells.
One aim is the long-term development of improved methods for cultivation and expansion of MSCs by the use of alternative materials, coatings, surface structuring or media additives in order to enhance their clinical applicability.
In cooperation with the department of rhino-oto-laryngology MSCs are modified with neurotrophic growth or transcription factors for use as a drug delivery device for cochlea implants or for a direct reprogramming into neuronal-like cells. Therefore the group is located within VIANNA (VerbundInstitut für AudioNeurotechnologie, NAnobiomaterialien und Lasermedizin, within NIFE): www.vianna.de.
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Weist, R., Floerkemeier, T., Roger, Y., Noack, S., Franke, A., Schwanke, K., Zweigerdt, R., Martin, U., Willbold, E.*, Hoffmann, A.* (2018): Differential expression of cholinergic system components in human induced pluripotent stem cells, bone marrow-derived multipotent stromal cells, and induced pluripotent stem cell-derived multipotent stromal cells. Stem Cells and Development 27, 166 - 183
Schulze, J., Kaiser, O., Paasche, G., Lamm, H., Pich, A., Hoffmann, A., Lenarz, T., Warnecke, A. (2017): Effect of hyperbaric oxygen on BDNF-release and neuroprotection: Investigations with human mesenchymal stem cells and genetically modified NIH3T3 fibroblasts as putative cell therapeutics. PLoS One, 12: e0178182
Rahim, M. I., Weizbauer, A., Evertz, F., Hoffmann, A., Rohde, M., Glasmacher, B., Windhagen, H., Gross, G., Seitz, J.-M., Müller, P. P. (2017): Differential magnesium implant corrosion coat formation and contribution to bone bonding. Journal of Biomedical Materials Research Part A 105, 697 - 709
Hoffmann, A., Floerkemeier, T., Melzer, C., Hass, R. (2017): Comparison of in vitro-cultivation of human mesenchymal stroma/stem cells derived from bone marrow and umbilical cord. Journal of Tissue Engineering and Regenerative Medicine 11(9):2565-2581 (Review)
Schäck, L., Budde S., Lenarz T., Krettek C., Gross G., Windhagen H., Hoffmann A.*, Warnecke A.* (2016):
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Roger, Y.,Schäck, L.M., Koroleva, A., Noack, S., Kurselis, K., Krettek, C., Chichkov, B., Lenarz, T., Warnecke, A.*, Hoffmann, A.* (2016):
Grid-like surface structures in thermoplastic polyurethane induce anti-inflammatory and anti-fibrotic processes in bone marrow-derived mesenchymal stem cells.
Colloids and Surfaces B: Biointerfaces; Vol. 148, p. 104 - 115
*: gleichwertiger Beitrag