Shear Stress Improves Stem Cell Attachment to Vascular Surfaces
DEVELOPMENT OF NOVEL VASCULAR BYPASS GRAFT ADULT STEM CELLS
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Released: Tue 13-May-2008, 16:30 ET
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A new study about how shear stress improves adult stem cell
attachment to vascular surfaces moves researchers closer to the
development of a unique tissue-engineered stem cell vascular bypass
graft.
Newswise — A new study about how shear stress improves adult stem
cell attachment to vascular surfaces moves researchers closer to the
development of a unique tissue-engineered stem cell vascular bypass
graft. The study will be presented during the Vascular Annual
Meeting, June 5-8, in San Diego, Calif.
At Thomas Jefferson University in Philadelphia, a team of researchers
lead by vascular surgeon Paul J. DiMuzio, MD, is developing a novel
vascular bypass graft using adult stem cells derived from a patient's
adipose tissue. According to Dr. DiMuzio, "The advantage of using
these stem cells is that they are easy to obtain in abundance from
patients in which they are intended for use; however, it has been
difficult to attach the stem cells to the surface of natural vascular
tissue grafts."
Work performed by Eric S. Hager, MD, directly addressed the problem
of stem cell attachment. "After we change (differentiate) the stem
cells into those resembling the lining of blood vessels (endothelial
cells), we seed them onto the grafts and slowly introduce shear
stress to improve their attachment," said Dr. Hager. "The current
study investigates exactly how shear stress alters the way the stem
cells adhere to vascular surfaces."
At the 62nd Annual Meeting of the Society for Vascular Surgery, Dr.
Hager and colleagues from Jefferson reported their work examining the
presence and function of molecules important for cell attachment
(called integrins) on the surface of the stem cells. The stem cells
express these important molecules, but at lower levels than found on
the endothelial cells they are attempting to emulate, possibly
explaining the initial difficulties in attachment. Others have
observed that endothelial cells increase integrin expression when
stimulated by shear force, enabling these cells to remain attached to
the inside of blood vessels.
In designing the current study, Dr. Hager hypothesized that "Shear
stress improves stem cell attachment to vascular basement membrane
components via upregulation of integrin expression, similar to
endothelial cells." According to Dr. DiMuzio, "Firm attachment of the
stem cells to the vascular graft would allow for the formation of a
confluent monolayer of cells in the hopes of improving graft
function."
During the study, the researchers exposed human adipose-derive stem
cells (ASC) differentiated towards endothelial-
physiological levels of shear stress. Subsequently, integrins
expression was measured along with cell attachment to culture plates
pre-coated with various vascular basement membrane components
(collagen I, fibronectin, gelatin).
They observed that the human ASC expressed integrins, but at reduced
levels compared to endothelial controls. Application of shear stress
significantly upregulated á5â1 integrin expression, but not that of
ávâ3. Demonstrating that this translates to a functional change,
shear stress significantly improved ASC attachment to pre-coated
plates, particularly those with collagen I and fibronectin, but not
uncoated control. Finally, blockade of the á5â1 integrin receptor
significantly eliminated attachment.
According to Dr. Hager, "these data suggest that shear stress may be
useful to improve the retention of stem cells to tissue engineered
vascular grafts. Future experiments will evaluate how well the stem
cell grafts function as a bypass for occluded arteries."
Grants awarded to Dr. DiMuzio from the National Institutes of Health,
American Vascular Association and the American Heart Association
funded this research.
About the Society for Vascular Surgery
The Society for Vascular Surgery (SVS) is a not-for-profit society
that seeks to advance excellence and innovation in vascular health
through education, advocacy, research and public awareness. SVS is
the national advocate for 2,400 vascular surgeons dedicated to the
prevention and cure of vascular disease. Visit the website at
http://www.Vascular
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StemCells subscribers may also be interested in these sites:
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