| Project 9 |
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The impact of the inflammatory fracture hematoma on mesenchymal stem cell function and fracture healingProf. Buttgereit (first supervisor), Prof. Duda (second supervisor), Dr. Kolar (mentor); Charité The bone healing process is influenced by many factors such as age or gender, but is also known to be often impaired in people suffering from autoimmune diseases as well as in the elderly who are known to have diminished functionality of the immune system. These facts suggest the quality of bone healing to depend on proper immune system functioning. However, the exact interplay of immune functions and bone regeneration is still unclear, especially with regard to the early fracture hematoma representing the inflammatory phase of fracture healing. In this early phase, oxygen supply is suggested to be impaired in the fracture gap which is predominantly due to the destroyed vascular network. These conditions are also faced by mesenchymal stem cells (MSC) which are known to contribute to successful and timely fracture healing. We therefore suggest hypoxia as a feature of the inflammatory phase to be among the crucial factors influencing MSC functioning (angiogenesis, chemoattraction, differentiation), and thus fracture healing. For these reasons we aim at investigating the impact of the fracture gap microenvironment on the capacity of MSC to migrate to the fracture site, to differentiate and their ability to form new vessels. The impact of human fracture hematomas, already identified inflammatory factors found in fracture hematomas and different bioenergetic conditions on MSC functions will be analyzed. Optimal fracture gap conditions will be identified. The results could contribute to the development of new treatment strategies via MSC cell-based or MSC impacting therapy to positively influence the bone-healing outcome. Kasper G, Dankert N, Tuischer J, Hoeft M, Gaber T, Glaeser JD, Zander D, Tschirschmann M, Thompson M, Matziolis G and Duda GN. Mesenchymal stem cells regulate angiogenesis according to their mechanical environment. Stem Cells 2007. 25: 903-910. |
