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.

Research topics

Graded implants

• 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.

More information on this project is presented here: www.mh-hannover.de/9825.html and www.gradierte-implantate.de

Optimization of neuroprostheses

• For further development of implantable neuroprostheses electrodes made from soft and biocompatible materials with optimal electrochemical properties have to be used. Aim of this DFG project which we perform in collaboration with the Laser Zentrum Hannover (Prof. B. Chichkov) and the institute of biophysics of LUH (Prof. A. Ngezahayo) therefore is to use polymers based on organic macromolecules for an enhancement of electrodes for neuroprostheses. This shall be achieved through three modules which incorporate novel approaches both from the material science and biological point of view: the preparation of electrochemically attractive polymers by use of metallic nanoparticles, surface microstructuring of these polymers, and the biological demonstration of neuronal activities in appropriate cell culture systems. For the in vitro cell studies the biological demonstration of neuronal activities and adequate cell adhesion will be performed with human MSCs since primary human nerve cells are hardly available. Mesenchymal stem cells respond to material properties and have an inherent potential for neuronal differentiation.

Regenerative strategies

• 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.