annual report 2011 - Office for Research - Northwestern University

Melina R. Kibbe
Feinberg School of Medicine
Stem Cells That Reside in the
Arterial Wall May Control the
Fate of Vascular Interventions
Failure of vascular interventions, such as
bypass grafting and balloon angioplasty
and stenting, results from neointimal
hyperplasia. Classically, this process has
been thought to result from overgrowth of the cells
that line the media—the middle layer of the arterial
wall—and that ultimately leads to restenosis and arterial
occlusion. In the last decade, however, this view has
been changing, as it is now recognized that the arterial
wall’s outer layer, the adventitial, may play a much
more prominent role in this process. Specifically, the
adventitia has been identified as home to a progenitor
cell, the Sca1+ cell, which may be integral to the process
of neointimal hyperplasia.
Melina Kibbe, vascular surgery, has had a long-
standing interest in the development and prevention
of neointimal hyperplasia. Her efforts have focused on
using nitric oxide as a therapeutic agent, given that nitric
oxide is a potent inhibitor of neointimal hyperplasia.
While studying the effects of nitric oxide on the
vascular wall, Kibbe discovered that following vascular
interventions, nitric oxide dramatically increases the
Sca1+ progenitor cells residing in the adventitia just
external to the external elastic lamina. Whether this
increase elicited by nitric oxide is due to an increase in
recruitment of these cells to the vascular wall following
injury or due to inhibition of phenotypic differentiation
of these cells to myofibroblasts, thereby preventing
them from contributing to neointimal hyperplasia,
remains to be determined.
Kibbe was recently awarded a grant from the National
Institutes of Health to study the role of Sca1+ cells
following vascular interventions and nitric oxide therapy.
Kibbe’s research has also been supported by grants from
the Department of Veterans Affairs, the American Heart
Association, the American Recovery and Reinvestment
Act, and the Northwestern Memorial Foundation.
Immuno�uorescent staining of Sca1+ cells in culture
Balloon angioplasty Balloon angioplasty + nitric oxide
Cross section of an artery that has undergone balloon angioplasty (left) and balloon angioplasty with
nitric oxide exposure (right)
Excellence in Research | Annual Report 2011 39
Andrew Campbell