Bioengineered Human Acellular Vessels as Dialysis Access Grafts

Abstract

Cardiovascular regenerative medicine has taken many avenues. One approach currently in clinical trials does not require any cells from the patient, and is an engineered tissue that is available “off‐the‐shelf”. Our approach to vascular engineering involves seeding allogeneic vascular cells onto a degradable substrate to culture vascular tissues in a biomimetic bioreactor. After a period of 8–10 weeks, engineered tissues are then decellularized to produce an engineered extracellular matrix‐based graft. The advantage of using allogeneic cells for graft production is that no biopsy need be harvested from the patient, and no patient‐specific culture time is required. These grafts are currently being tested in a Phase III clinical trial in Europe and in the US. Early experience supports the potential utility of this novel tissue engineered vascular graft to provide vascular access for hemodialysis.The decellularization approach has also allowed us to generate scaffolds to support whole lung regeneration. Using rat, porcine and human sources of organs, lungs have been subjected to a range of decellularization procedures, with the goal of removing a maximal amount of cellular material while retaining matrix constituents. Next‐generation proteomics approaches have shown that gentle decellularization protocols result in near‐native retention of key matrix molecules involved in cell adhesion, including proteoglycans and glycoproteins. Repopulation of the acellular lung matrix with mixed populations of neonatal lung epithelial cells results in regio‐specific epithelial seeding in correct anatomic locations. Survival and differentiation of lung epithelium is enhanced by culture in a biomimetic bioreactor that is designed to mimic some aspects of the fetal lung environment, including vascular perfusion and liquid ventilation. Current challenges involve the production of a uniformly recellularized scaffold within the vasculature, in order to shield blood elements from the collagenous matrix which can stimulate clot formation. In addition, we have developed methods to quantify barrier function of acellular and repopulated matrix, in order to predict functional gas exchange in vivo.Support or Funding InformationNIH R01 HL127386 (Niklason)