Joint BME and Material Science Seminar: Laura Niklason, M.D., Ph.D.

Progress in Vascular and Lung Engineering

Professor of Anesthesiology & Biomedical Engineering, Yale University

Abstract

Our laboratory has been working in vascular and lung regeneration for a number of years. Our work is showing that arteries, which are connective tissues, may be successfully replaced using engineered extracellular matrix scaffolds that are essentially acellular. These tissues remodel in vivo and do not excite a significant inflammatory response, which may be related to their low rates of thrombosis and intimal hyperplasia. In addition, because decellularized grafts can be made from allogeneic cells and stored until time of need, the heretofore long culture times needed for autologous artery production become moot. Hence, this approach may take us one step closer to off-the-shelf arterial grafts for humans.

To explore whether lung tissue can be regenerated in vitro, we treated lungs from adult rats using a procedure that removes cellular components but leaves behind a scaffold of extracellular matrix that retains the hierarchical branching structures of airways and vasculature. We then used a bioreactor to culture pulmonary epithelium and vascular endothelium on the acellular lung matrix. The seeded epithelium displayed remarkable hierarchical organization within the matrix and the seeded endothelial cells efficiently repopulated the vascular compartment. In vitro, the mechanical characteristics of the engineered lungs were similar to those of native lung tissue, and when implanted into rats in vivo for short time intervals (45-120 min), the engineered lungs participated in gas exchange. Although representing only an initial step toward the ultimate goal of generating fully functional lungs in vitro, these results suggest that further investigation of this approach is warranted.