Focus of our Research group
Repair of bone defects in the craniomaxillofacial area poses major socio-economic challenges. Treatment may be enhanced via an engineered graft containing osteoinductive factors and synthetic osteoconductive carrier such as calciumphosphates and chitosan. These carriers have similar properties and composition as bone mineral. Extracellular vesicles (EVs play a key role in cell-to-cell communications). It is proposed that EVs derived from bone cells promote osteogenic differentiation in mesenchymal stem cells (MSCs). In combination with osteoconductive carriers, EVs have the potential as therapeutic tools in bone tissue engineering. The mechanisms of their activity will be further studied in this project.
Stem cells have evoked novel possibilities in the field and the number of clinical applications combining stem cells with biomaterials is rapidly increasing. Ongoing clinical trials will generate valuable information on the risks of these new strategies; however, cutting-edge science and prognostic safety assays to predict the risk factors prior to surgery are urgently called for. Our aim is to contribute to the development of robust in vitro assays for the evaluation of safety of stem cell therapies in the CMF area.
It has become increasingly apparent that secretion products of stem and progenitor cells is responsible for many of the observed effects of stem cell therapies. These paracrine factors secreted by stem- and progenitor cells, like growth factors and cytokines, are of major interest to discover new therapeutics that stimulate local tissue regeneration for the use in tissue engineering. EV are part of the paracrine factors that also play an important role in local induction of tissue regeneration.
Extracellular vesicles are lipid membrane vesicles, containing a variety of RNA species (including mRNAs, miRNAs), soluble (cytosolic) proteins, and transmembrane proteins. Extracellular vesicles are able to affect cell phenotype, recruitment, proliferation, and differentiation in a paracrine manner. These paracrine effects of EV have a potential benefit in regenerative medicine. EV can be incorporated in regenerative therapies, for example by (co-)injection, mixing with hydrogels, or coating scaffolds with EV using fibrin gels or specific linkers. (adapted from; De Jong et al. Front Immunol. 2014;5:608.)
Applications of EV in regenerative medicine.
After isolation (A), EV could be utilized in regenerative medicine through a number of methods, either separately or in combination with cells or other therapeutics. (B) Direct injection into tissue or circulation. (C) Mixing of EV in hydrogels. (D) Coating electrospun fibers indirectly via chemical linkers, antibodies, or specific tags engineered on to the EV. (E) Coating of electrospun fibers with bio-degradable gels such as fibrin, resulting in gradual release during gel degradation. (adapted from; De Jong et al. Front Immunol. 2014; 5:608. doi:10.3389/fimmu.2014.00608)