Decellularization in Blood Vessel Transplants

Given a donor blood vessel, researchers can strip it of its cells to leave just the extracellular matrix structure. This can then be repopulated with a patient's own cells, making it possible to transplant the blood vessel without risk of rejection. This is one of a number of applications of decellularization demonstrated in human trials in recent years:

Our study is a proof-of-concept clinical report of the successful recellularisation of two decellularised human blood vessels with autologous whole peripheral blood, which were subsequently used for a bypass procedure in two patients with portal vein thrombosis without the need for immunosuppression. The work is important conceptually because it provides early evidence for generating clinically useful personalized blood vessels using a simple blood sample from the patient.

Vascular diseases are increasing health problems affecting more than 25 million individuals in westernized societies. Such patients could benefit from transplantation of tissue-engineered vascular grafts using autologous cells. One challenge that has limited this development is the need for cell isolation, and risks associated with ex vivo expanded stem cells. Here we demonstrate a novel approach to generate transplantable vascular grafts using decellularized allogeneic vascular scaffolds, repopulated with peripheral whole blood (PWB) in vitro in a bioreactor. For clinical validation, two autologous PWB tissue-engineered vein conduits were prepared and successfully used for by-pass procedures in two pediatric patients. These results provide a proof of principle for the generation of transplantable vascular grafts using a simple autologous blood sample, making it clinically feasible globally.

In the present and other currently ongoing studies we have successfully recellularized veins using blood from individuals and patients in the age range of 4-55 years. However, it is reported that the numbers of circulating stem/precursor cells is decreased in patients with diabetes and end-stage renal diseases. So it remains to be tested whether this method would work in such patients. We did not detect any HLA antibodies after transplantation indicating satisfactory decellularization of the blood vessels. Both patients have been transplanted on compassionate grounds and therefore optimization of the technique has been on a "patient to patient" basis. We are currently seeking permits to carry out a clinical trial, which will include a larger number of patients to determine the efficacy of grafting tissue-engineered veins as vascular replacement therapy.

Link: http://dx.doi.org/10.1016/j.ebiom.2014.09.001

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