Grants Funded

Abstract
The long-term goals of our research are to understand and control the process of postoperative adhesion formation and to develop a transplantable tendon using host-derived adult stem cells in order to overcome the two major clinical problems in tendon surgery today: postoperative adhesions and lack of suitable graft material.

Aim 1: Our first goal is to investigate the role of the highly conserved Notch signaling pathway in the context of tendon healing. Knowledge about the molecular mechanisms of adhesion formation is growing constantly, but so far research has focused on growth factors and signaling pathways that are related to wound healing. Notch signaling has been associated with cell cycle control, differentiation and migration of cells in various cell lines. In contrast to the previous approaches studied in tendon healing and engineering, the pathway is depending on cell-to-cell interaction rather than signal transduction by soluble ligands. The involvement of the Notch signaling pathway in collagen production and remodelling will be first investigated in vitro in rabbit derived tendon and tendon sheath cells. Then the role of the pathway will be characterized and ultimately modulated after tendon surgery in a rabbit model in vivo.

Aim 2: We will characterize the role of Notch signaling in the process of tendon differentiation of human adipose derived stem cells. Although there are reports on successful engineering of tendon and tendon-like tissue, the knowledge about molecular mechanisms in tendon differentiation is scarce. As there is increasing evidence that Notch signaling contributes to the maintenance and proliferation of adult stem cells. we hypothesize that differentiation of stem cells into tenocytes. We will study notch signaling in bioreactor that induces differentiation of stem cells to tenocytes by mechanical stimulation.

Our research might contribute to develop new strategies to overcome the major clinical problems of tendon surgery today.

Biography
Kai Megerle was in born in 1976 in Bayreuth, Germany and received his medical degree from the Technical University of Munich, Germany after completing his doctoral thesis at the Institute for Experimental Oncology and Therapy Research evaluating improved gene transfer delivery systems. During his final year at medical school he was awarded a traveling scholarship to visit the departments of Plastic Surgery at the Memorial Sloan Kettering Cancer Center, New York, NY and MD Anderson Cancer Center, Houston, TX. He completed his residency in Plastic Surgery at the University of Heidelberg, Germany at the BG Trauma Center Ludwigshafen. He is specifically interested in hand surgery both on a molecular level and in clinical research and is the 2009 traveling scholar of the German Society of Plastic Surgeons (DGPRAC). He is currently preparing a postdoctoral research fellowship at the Southern Illinois University School of Medicine and the Stanford University Medical Center.