Laura Niklason, MD, PhD

Vice-Chair for Research, Associate Professor, Dept. of Anesthesiology & Biomedical Engineering

Dr. Niklason's research program focuses on cardiovascular tissue engineering, and on mechanical characteristics of native and engineered vascular structures. General research projects involve the culturing of implantable engineered arteries, and on the development of microvasculature in vitro. During the past year, we have had several exciting accomplishments. Specifically, we've shown the feasibility of deriving differentiated vascular smooth muscle cells from monocyte fraction of adult human bone marrow. We've shown that these cells, when exposed to local stimuli resident in the injured vascular wall, such as cyclic mechanical strain, TGF-beta1, and certain matrix substrates, express early and mid-markers of smooth muscle differentiation. It appears the serum response factor is involved in the signaling of this process, that occurs between 7-14 days of culture. Current studies are directed at teasing out the signaling events, as well as assessing the utility of such cells in engineered vascular constructs. In addition, we are examining the potential role of mesenchymal-derived smooth muscle cells in the formation and stabilization of microvessels in vitro.

In addition to these topics in cardiovascular tissue engineering, we are exploring potential mechanisms that may contribute to the syndrome of delayed crebral vasospasm that follows subarachnoid hemorrhage. Pursuant to this, we are conducting studies of changes in the mechanical properties of cerebral arteries that are exposed to clotted blood. Currently, we are working with our collaborator, Dr. Jay Humphrey, to define temporal patterns of growth factor release from clot, in order to provide input data for constitutive mathematical models of changes in vessel mechanics over time. These modeling and in vitro studies will be supplemented with in vivo studies in large animals, using induced subarachnoid hemorrhage and quantifying vessel mechanics over the course of vasospasm.