2008 Faculty Researchers

Dmitri Baklanov M.D., Ph.D.

Vasculogenic properties of embryonic proepicardial cells

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Department

Internal Medicine, Division of Cardiovascular Medicine

Office Location

MC314

Phone #:

Office: (573) 882-2296
Fax: (573) 884-7743

Summary

What makes some patients with coronary artery disease (CAD) develop protective collateral vessels in response to myocardial ischemia? This is one of the questions that interested students can help to answer working with researchers in the Division of Cardiovascular Medicine. In situ assembly of precursor cells forming luminal structures is the mechanism of embryonic coronary artery vasculogenesis. A transient extracardiac structure on the side of sinus venosus, proepicardium (PE), is established as a source of coronary endothelial and supporting cells. We have isolated PE cells of chick embryos at Hamburger and Hamilton stages 14-21 and expanded them in cell culture conditions designed to grow human umbilical vascular endothelial cells (HUVEC). The growth kinetics and morphology of PE cells suggest the possibility that they are stem cells. The cells maintained in culture express several endothelial marker genes (Flk1, PECAM, Ve-Cadherin), vWF protein, as well as pericyte-smooth muscle marker genes. When suspended in 3D collagen type I gels and stimulated by a combination of growth factors, the PE cells undergo morphogenesis and assemble into vascular-like structures.

The initial goal of my research studies is to focus on the primary isolation of avian embryonic PE cells, their molecular characterization under conditions favoring endothelial specification. The overall goal is to evaluate the functional properties of cultured PE cells (and later vasculogenic cells of clinically relevant origin) in 3D extracellular matrix assays. The proposed research has potential for translational development of novel strategies to prevent and treat ischemic heart disease. There has been considerable interest in the use of cell-based approaches to stimulate blood vessel growth in patients with ischemic heart disease. To date, these studies have not been highly successful. I postulate that studies, like mine, aimed at defining how coronary arteries develop embryologically, are essential to the development of cell-based therapies for cardiovascular repair. I have previously participated in studies of gene and cell delivery for myocardial repair in ischemic heart disease, both in large animal models and in clinical trials.