Development of a multi cellular in vitro model to study protective and regenerative therapy strategies ofchronically cutaneous wounds

点击翻译按钮获取中文摘要

Irradiation may lead to a compromise in cutaneous wound healing with important clinical consequences, ranging from pathological scarring to life threatening arrosion of major vessels requiring extensive reconstructive efforts.The mechansims involved in pathological wound healing are complex and incompletely understood.Therapeutic interventions to enhance the wound healing process are scarce, poorly researched and have not been conclusively shown to improve the clinical outcome. These include various pharmacological interventions as well as stem cell transplantation. No in vitro model exists that adequately reflects the pathophysiology of compromised wound healing. An important limitation inherent to established models is that they do not integrate the multiple cell types and their inter-cellular interactions affecting the wound healing process.The development of an in vitro wound healing model, which simulates the effects and adverse responses to external radiation on the wound healing process and allows to investigate the effects of therapeutic intervention is hence the goal of the present project.The planned project is aimed to develop a multi cellular in vitro model, which mirrors the pathophysiological processes of cutaneous wound healing better than previously described mono-cellular models. Key aspects of chronic wound healing compromise include atrophy and ulceration. These two aspects correlate with two key cell types: fibroblasts and endothelial cells, which will hence be integrated in the present model.Human adipogenic stem cell transplantation is the most promising therapeutic intervention available and will be integrated in the planned model as well. Their therapeutic effect has been described to be optimized with pharmacological modulation. Hence the effects of pharmacological modulation are to be investigated in the present model as well.Our preliminary data suggest that pro-inflammatory cytokines, such as interleucine-6 and markers of microcirculation, like soluble adhesion molecules ICAM-1 and VCAM-1, are of special relevance for the generation of radiation induced wound healing compromise. These and other markers will serve to quantify the effects of irradiation and pharmacological modulation on radiation-induced wound healing compromise in a multi-cellular in vitro model.