Repair of bone defects in the craniomaxillofacial area remains challenging. Treatment may be enhanced via an engineered graft containing osteoinductive factors and synthetic osteoconductive biomaterial scaffolds. Extracellular vesicles (EVs) play a key role in cell-to-cell communications. It is proposed that EVs derived from osteoblasts promote osteogenic differentiation in mesenchymal stem cells (MSCs). Also in bone pathology, e.g. osteosarcoma (OS), EVs could be implicated in the progression of OS and the conditioning of its microenvironment as well as its metastasis. The tumour engineering strategy is considered as a potential platform to investigate the dynamics of OS development and progression, and to develop clinically relevant models for targeting OS and OS stem cells.
MSCs 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 appreciated that the secretome 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. EVs are part of the paracrine factors that also play an important role in local induction of tissue regeneration as well as pathology development and fate.
Extracellular vesicles (EVs) have received considerable interest in the past decade as a major contributor to intercellular communication in normal homeostasis as well as in pathological conditions. Osteosarcoma is the most common form of primary bone malignancy and a major cause of cancer-related death in adolescents and young adults. However, osteosarcoma remains challenging to study due to the complexity of its microenvironment and related cellular heterogeneity. Currently, we are developing novel approaches for studying osteosarcoma interactions with its microenvironment, via EVs and secreted factors. By employing a combination of next generation sequencing (NGS), methylation analysis, and proteomics approaches, we aim to dissect these interactions to gain a better understanding of the clinical behavior of osteosarcoma and to improve treatment outcomes.
While our earlier studies are based on commercial osteosarcoma cell lines, we have recently started working with human and canine osteosarcoma samples. Osteosarcoma has much higher incidence in dogs yet has similar biological and clinical characteristics as in humans.
We have developed preclinical large animal models for testing novel reconstructive approaches of craniomaxillofacial bone defects. Additionally, we are addressing the vascularization challenges for tissue engineered bone constructs, therefore, we have been interested in the in vitro activation of HIF-1α/VEGF pathway in adipose tissue-derived mesenchymal stromal cells (AT-MSCs), and also the application of the in vivo bioreactor techniques in an ovine model.
Three-dimensional (3D) tissue models are an attractive system to study diseases and other biological phenomena. We are developing 3D models of osteosarcoma designed to obtain more accurate drug cytotoxicity responses, compared to two-dimensional models. Our approach involves a combination of biomaterial scaffolds, hydrogels and self-assembling spheroids.
We are thankful to the following foundations and organizations for helping us sustain our research.