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Restoring organ function by means of regenerative medicine (REGENERATE)

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This programme focuses on various aspects of tissue (re) generation, repair and remodelling, including inflammation.​

Programme Leaders   Mission  

REGENERATE brings together a multi-disciplinary team of researchers and clinicians that share an interest in regenerative medicine in the broadest sense. The programme serves to facilitate interactions between these scientists through various means to foster cross-disciplinary thinking and to encourage collaborative science on the topic of regenerative medicine from bench to bedside. Importantly, the programme aims to bridge fundamental and translational research to expedite the development of regenerative medicine therapies in the (near) future. While all REGENERATE scientists have their own research interests related to regenerative medicine, the REGENERATE programme helps the participating scientists to connect to other REGENERATE scientists through sharing and exchanging relevant technology, expediting new technology development for future regenerative medicine therapies.

Description of the Programme  

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.

Fibrosis

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.

Relevance to Healthy Ageing  

Trauma, disease, and ageing can leave critical defects that the body cannot heal by itself.  Using a combination of cells, bioactive molecules, biomaterials, and mechanical conditioning, regenerative medicine seeks to achieve functional restoration of tissues and organs.  Regenerative medicine will help extend healthy longevity through tissue repair and ultimately through tissue/organ replacement. Ageing can be viewed as precursors of disease and disabilities of that come with advancing age: a set of side-effects of normal metabolism that accumulate throughout life and eventually impair and overwhelm our biology. The use of proper biomaterials is expected to play a key role in improving patient care in the near future, especially in relation with tissue loss or dysfunction. The shift from tissue removal to tissue replacement and tissue regeneration is driven by the evolution of biomaterials from bioinert to bioactive and bioresorbable associated with advances in molecular biology, and by the increasingly complex biomedical problems of an ageing and more active population.

Principal Investigators