We propose a novel approach to treat insufficient venous flow. It relies on the use of minipumps made of engineered cardiac muscle. If successful, this approach has the potential to revolutionize the treatment of chronic venous disease and other causes of limited flow, including direct injury and paralysis of lower limb muscles. Specifically, our long term goal is use a patient's stem cells to create a rhythmically beating sheath of cardiac muscle cells that surrounds medium-sized veins. These 'Cardiomyocyte-based Venous Assist Devices or CMVAD will aid flow without requiring recreation of the heart's structural complexity. The main goal of this application is to obtain proof-of-the concept data for this novel approach using rat neonatal cardiomyocytes and human embryonic stem cell derived cardiomyocytes. Experiments will be structured along two specific aims. The first specific aim is to test the ability of CMVAD o create pressure within close-ended excised segments of canine, porcine or human saphenous veins and to examine how much the electric and mechanical stimulation of CMVAD improves its physical strength and force of contraction. The second specific aim is to a) compare different CMVAD designs for their ability to continuously propel fluid thru an excised vein segment with functional unidirectional valve and b) test feasibility of peristaltic fluid propulsion by electriclly stimulating a downstream end of an elongated CMVAD sleeve placed around vein segment without functional valve. To the best of our knowledge the proposed methodology would be one of the first examples of using tissue engineering protocols not just to repair damaged organs but to design entirely new ones - either outside the organ's original anatomical location or using the functionality of specialized cells from different tissues.
We propose to create a regularly contracting layer of cardiomyocytes around vein segments of lower extremities with the goal of aiding venous return and treating chronic deep venous insufficiency. The proposed approach opens up doors to the development of a new treatment strategy to millions of patients suffering from chronic venous disease.
