Arterial tissue engineering : influence of shear stress on endothelial progenitor cells

  • Arterielles Tissue Engineering : Einfluss von Scherstress auf endotheliale Progenitorzellen

Olszewski, Sebastian Lukasz; Jockenhövel, Stefan (Thesis advisor)

Aachen : Publikationsserver der RWTH Aachen University (2013)
Dissertation / PhD Thesis

Aachen, Techn. Hochsch., Diss., 2013


Despite the immense progress in established surgical therapies, cardiovascular diseases remain the leading cause of death in the Western society. Coronary artery bypass surgeries or balloon angioplasties represent the gold standard for cardiac infarction cure. Unfortunately, these procedures have drawbacks that make alternative approaches inevitable. Artery bypass surgery is invasive and requires withdrawal of intact vessels from the patient’s peripheral circulation. This restricts the number of realizable bypasses. Balloon angioplasty destroys the vessel’s inner layer of endothelial cells (ECs) and promotes thrombus formation. Tissue engineering (TE) combines cells, scaffolds and signalling molecules to cultivate substitute organs or tissues. A completely autologous graft can be grown using fibrin gel from the patients’ own blood as scaffold. Endothelial cells represent the cell source of choice for the lining of the graft at the moment. Unfortunately, ECs are isolated from a biopsy of the patient and require invasive surgery. With the aim to avoid this, endothelial progenitor cells (EPCs) were evaluated as alternative cell source for arterial tissue engineering. These cells can be isolated from patients’ blood and are able to differentiate into an endothelial-like cell type. As the response of ECs to shear stress is one of their crucial functions, it is essential to know how EPCs respond to this stimulus when aiming to use them as alternative. In the present study two shear stress bioreactor systems were used to simulate different flow conditions. With a novel Taylor-Couette flow based system steady laminar and turbulent flow were generated while a parallel flow chamber served for pulsatile laminar flow. So could not only conditions of healthy individuals be simulated but also pathophysiological conditions with turbulence that appear at anastomoses of graft surgery patients. The present study demonstrates how EPCs lose their endothelial-like phenotype through exposure to shear stress. These findings are supported by the outcome of experiments in which ECs and EPCs were compared directly as lining of a tissue engineered construct. After stimulation of the construct in a conditioning bioreactor ECs had formed a confluent cell layer while EPCs failed. Taken together, the results from this study inquire the suitability of EPCs as EC substitute in arterial TE. Nevertheless, considering the potential of EPCs reported in literature, further studies will be necessary for a final conclusion on this issue. A completely new pulsatile Taylor-Couette shear stress bioreactor system was also developed during this study and will facilitate to answer open questions in this regard in future.