Regenerative medicine aims at the generation of functional biological tissues for the replacement of diseased or impaired tissues. To do so, often (stem) cells are used in combination with a degradable biomaterial that serves as a temporary scaffold and which is replaced by the tissue in question. Tissue damage and biomaterials implanted into the body invariably evoke an inflammatory response, which sets the stage for tissue repair. The progression from inflammation to repair should be regulated in such a way that tissue repair is adequate, but often aberrant inflammation will lead to fibrosis.
The research programme focuses various aspects of stem cell biology, differentiation towards various tissue types, tissue (re)generation, repair and remodeling, including inflammation.
Our main research questions are:
- What is the role of key cellular and molecular players in determining the balance between inflammation, physiologic repair and aberrant repair (fibrosis)?
- How can we orchestrate the tissue microenvironment in order to promote repair and/or prevent fibrosis?
- How can we translate basic insight into above aspects into new therapeutic approaches (e.g. by means of smart biomaterials / drug delivery)?
In addition to these main research questions, REGENERATE aims to bring together scientists form various disciplines to implement and develop new technologies for stem cell biology for regenerative medicine purposes. The UMCG iPSC/CRISPR centre is an important asset for this and serves as a meeting hub for REGENERATE-associated researchers.
Organ and tissue repair
Organ and tissue damage invariably leads to inflammation, which makes way for tissue repair. The interplay between inflammatory cell subsets dictates the outcome of inflammation, but is poorly understood mechanistically. Therefore, more fundamental research is necessary into research questions concerning the cellular composition of inflammatory processes in settings of organ damage and the in vivo foreign body reactions, the cellular plasticity of macrophages, the modulation of the transition from inflammation to repair, the possibilities to use local drug delivery in order to achieve reparative outcomes, and even the difference between fetal and adult wound healing.
The foreign body response
With the implantation of materials the non-specific immune system will start the foreign body response (FBR). Macrophages are key players in the FBR, as well as the giant cells that are formed by means of fusion of macrophages. Controlling the activation of macrophages and the formation of giant cells are powerful tools to modulate the FBR, thereby improving regenerative strategies to repair tissues. Therefore, also here macrophages are the focus of our attention, including the role of macrophage subsets, the molecular basis of macrophage fusion, the molecular basis of collagen degradation by macrophages and giant cells, their communication with fibroblasts, the role of fibroblasts in collagen deposition (capsule formation; stromal formation), and the role of physical and chemical parameters of biomaterials on the onset and evolution of the foreign body reaction.
Within the two research areas described above fibrosis is a unifying factor. Fibrosis also is the pathological outcome of wound healing processes in a variety of organs (e.g. heart, liver, lung, kidney, skin) through the deposition of an excessive amount of collagen, being the hallmark of fibrosis. The pathogenesis of fibrosis remains poorly understood, mainly because it is unknown what subsets of fibroblasts are involved in collagen deposition. Also the role of collagen-modifying enzymes in fibrosis is poorly understood. Therefore, understanding the pathways leading to an excessive accumulation of collagen can help to define intervention points for novel therapeutics to benefit regenerative medicine approaches as well as to prevent organ-related fibrosis. In fact, therapy will be targeting the amount of collagen deposited.