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Research
Interests
Maintenance of facular cell function is critical for the survival of tissues and organs. A number of factors alters vascular cell function, leading to the development of vascular disorders. Flow and the associated shear stress have been shown to play an active role in the regulation of the structure and function of vascular system. Another force that alters cellular function is gravity. Gravity presents a special challenge to the vascular system in that vessels are constantly working against gravity to keep blood flowing to the head. Whereas in space, gravity is greatly reduce (microgravity) and the vessels do not have to labor against gravity to distribute blood. Therefore, the overall objective to this study is to understand how the vasculature adapts to the absence of gravity. One of the questions that needs to be answered is why persons that have been in a microgravity environment have difficulty maintaining their blood pressure when standing after returning to Earth’s gravitational force. Sine only a limited number of studies can be conducted in space, there is a great need for research that addresses this and other questions using ground-based models.
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This
study involves the use of cells isolated from blood vessels,
specifically endothelial cells. These cells are grown
in a rotating bioreactor. This equipment developed by
NASA simulates much of what occurs in microgravity. We
cannot reproduce what is found in microgravity, but with
this system we provide a unique environment that provides
low sheer conditions and allows for high mass transfer
and freedom of assembly.
Such
an environment induces spontaneous differentiation because
it provides cells with the ability to grow in three
dimensions. We characterized bovine aortic endothelial
cells (BAEC) continuously cultured in the rotating wall
vessel (RWV) bioreactor for up to 30 days.
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grew as multi-bead aggregates consisting of 3-12 beads
after 8 days, ~ 20 bead aggregates after day 16 and as
larger tissue-like aggregates after 30 days. There appeared
to be a layer of BAEC growing around the aggregates after
8 days. Single beads covered with confluent BAEC displayed
the typical endothelial cell morphology. However, after
30 days, very large multi-bead aggregates with a smoother
surface formed. |
For
clear viewing of BAEC around the surface of the beads, cultures
grown as single of multi-bead aggregates were cut as histological
sections and stained with toluidine blue. All cultures were
positive for von Willebrand Factor, with no differences noted
for cells in the RWV rotating at different rates. Cells growing
between and around beads were also positive for this endothelial
cell marker.
Relevant
Publications
Dutt, K., Harris-Hooker, S., Ellerson, D., Layne, D., Hunt, R. Generation of 3D Retina like Structures from a Human Retinal Cell Line in a NASA Bioreactor. Cell Transplantation 2:717-731, 2003.
Dutt, K., Harris-Hooker, S., Sanford, G., Brako, L., Ravindra, K., Sroufe, A., and Melhado, C. “Three-dimensional model of angiogenesis: Co-culture of human retinal with bovine aortic endothelial cells in the NASA bioreactor. Tissue Engineering 9:893-908, 2003.
Sanford , G., Ellerson, D., Mehado-Gardener, C., and Harris-Hooker, S. 3D growth of endothelial cells and the microgravity-based rotary wall vessel bioreactor. In Vitro Cell Devel. Biol. 38:493-504, 2002.
Quaye, E., Alema-Mensah, E., Omeogu, C., Alvarez, D., Dwamena, F., and Harris-Hooker, S. Lack of adequate attention to elevated blood pressure in an urban hypertensive population. Ethnicity and Disease 11:454-463, 2001.
Harris-Hooker, S., Ellerson, D., Bosah, F., and Sanford, G.L. Bradykinin stimulation of endothelial cell nitric oxide production is mediated by actin organization and glucose concentration. Ethnicity and Disease 11:365, 2001.
Keywords
Vascular
remodeling, Hypertension, Hypergravity, Hypogravity
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