Carsten Werner

Bioartificial stem cell microenvironments

Previous and current research

Fate decisions of stem and progenitor cells are controlled by environmental switches. Biomimetic concepts of materials and surface science can be instrumental to identify and modulate the related exogenous signals. Using an orchestrated set of design approaches we work to develop polymeric substrates providing physical and biomolecular cues of stem cell niches:

(i) micropatterning of surfaces and generation of lateral gradients by soft lithography and microfluidic tools

(ii) cell-free and cell-driven in vitro reconstitution of ECM assemblies (collagen I based fibrils containing glycosaminoglycans; collagen IV/laminin networks)

(iii) synthesis of biohybrid matrices (e.g. consisting of heparin and starPEG molecules) with varied pliability

(iv) covalent immobilization of growth factors/cytokines (e.g. LIF) via reactive polymer coatings

(v) molecular imprinting of chemokines (e.g. SDF-1α) in polymer hydrogels.

Interactions of the biomimetic polymer substrates with hematopoietic and mesenchymal stem cells are explored with dedicated biophysical experiments (time lapse studies, confocal laser scanning and scanning force microscopy to unravel the mechanisms of cell-matrix adhesion), immunophenotyping (flow and laser scanning cytometry), culture/ differentiation assays and gene expression analysis.

Human hematopoietic stem cells on a elastomeric film with microcavities (left) and within a fibrilar collagen I/heparan sulphate matrix (right)

Future prospects and goals

Future projects aim at the variation and adaptation of biomimetic substrates and matrices during time and under the action of environmental or cell-derived stimuli. Our goal is to contribute to the refinement of the hypotheses on exogenous signals of the stem cell niche which, in turn, will provide a base for the development of a new generation of biomaterials for stem cell bioengineering.

About

1998: PhD, Dresden University of Technology 1995-2000: Group Leader, Leibniz Institute of Polymer Research Dresden since 2000: Head of Department Biomaterials, Leibniz Institute of Polymer Research Dresden/ Max Bergmann Center of Biomaterials since 2000: Adjunct Professor, Institute of Biomaterials and Biomedical Engineering, University of Toronto

Selected publications

Werner, C., Pompe, T., Salchert, K. (2006): Modulating extracellular matrix at interfaces of polymeric materials. Advances in Polymer Science; 203.

Oswald, J., Steudel, C., Salchert, K., Joergensen, B., Thiede, C., Ehninger, G., Werner, C., Bornhauser, M. (2006): Gene-expression profiling of CD34+ hematopoietic cells expanded in a collagen I matrix. Stem Cells; 24: 494-500.

Pompe, T., Renner, L., Werner, C. (2005): Nanoscale features of fibronectin fibrillogenesis depend on protein-substrate interaction and cytoskeleton structure. Biophysical Journal; 88: 527-534.

Oswald, J., Boxberger, S., Joergensen, B., Feldmann, S., Ehninger, G., Bornhäuser, M., Werner, C. (2004): Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 2004; 22: 377-384.

Salchert, K., Streller, U., Pompe, T., Herold, N., Grimmer, M., Werner, C. (2004): In vitro reconstitution of fibrillar collagen type I assemblies at reactive polymer surfaces. Biomacromolecules 2004; 5: 1340-1350.

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