Influence of Endothelial Progenitor Cells (EPC) on revascularization of microvascular flaps in a small animal model.

• Applicant: Dr. Andreas Max Pabst
• Subject Area: Dentistry, Oral Surgery
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 241354483

In connection with defect reconstructions after traumata or radical tumor surgery microvascular flaps, e.g. the forearm- or the latissimus flap, became as far as possible accepted opposite to the pedunculated flaps in Oral- and Maxillofacial Surgery. A failure can maintain in a complete damage of the microvascular transplant and can result in a immediate explant of a second microvascular flap constituting a significant stress for the affected patients. Risk factors for a flap damage are beside thromboses of the arterial and venous flap vessels predominently earlier operations in the neck, arteriosclerosis and an irridation in the head and neck region. A possible supportive therapy option might be Endothelial Progenitor Cells (EPC). This unipotent stem cells can differentiate into adult endothelial cells within the scope of wound healing and in this manner ,in connection with the neovascularization, initiate the building of new blood vessels also in already necrotic areas.Aim of this study is to investigate the influence of human EPCs on revascularization and wound healing of microvascular flaps with the aid of a microvascular anastomosed free pectoralis skin flap in a small animal modell in rats.In own preliminary studies we could demonstrate a strong proangiogenic effect of EPCs with the help of different in-vitro and in-vivo angiogenesis assays. In addition we demonstrated that the application of human EPCs outclass the application of proangiogenic growing factors (VEGF+bFGF+PDGF) concerning their proangiogenic effect in a normoglycemic and a diabetic wound healing model in mice.Beside to the immunohistochemical detection of the revascularization in the flap, different ways of the secondary angiogenesis, e.g. sprouting angiogenesis vs. intussusceptive angiogenesis (IA) should be detected by characteristic features like the sprouts as a quality of the sprouting angiogenesis and pillars as a quality of the IA by means of SEM (Scanning Electron Microscopy) on three-dimensional corrosion casts. In order to detect also a functional parameter next to the revascularization coming up to the quality and the biomechanical capacity of the wound healing ,being inseperable connected with the revascularization, samples of the ingrown microvascular flaps will be tested by a tensile elongation measurement.Such information might be important for the prophylaxis and therapy of necrotic or insufficient microvascular flaps. Maybe EPCs could be used as a local or systemic applied supportive therapy option at risk patients or at a beginning necrosis of a microvascular flap.

• DFG Programme: Research Grants
• Participating Persons: Dr. Maximilian Ackermann; Professor Dr. Bilal Al-Nawas; Professor Dr. Moritz A. Konerding (†); Privatdozent Dr. Thomas Ziebart