Cardiovascular Diseases Clinical Trial
Official title:
OR-DRPD-SRI/CASIS2016: The Role of the Space Environment on Vascular Endothelial and Smooth Muscle Cell Processes
By studying the affect of the space environment on vascular cell types, our goal is to elucidate the mechanism of vascular cell damage in the space environment by exposing vascular cells to space flight. In this pilot study, The study team propose to assess changes in transcriptomics of vascular cell types in space compared to those in a ground based study.
Under conditions of simulated microgravity, it is well known that normal cellular processes
of vascular cells are altered. While these studies provide important information about these
alterations in cells, it is likely not a complete picture due to the limitations of ground
based simulated microgravity. It is our hypothesis that real microgravity, as is experienced
in space, will reveal changes in EC and SMC phenotype and function that alters cell-cell
communication. The study team will test our hypothesis by culturing mature endothelial cells,
as well as stem cell derived endothelial cells, and mature smooth muscle cells in low Earth
orbit (LEO) on the International Space Station (ISS) U.S. National Laboratory. The specific
aims the Study team have proposed are the following:
Specific Aim #1: Preflight isolation and characterization of circulating stem cell derived
endothelial cells. Specifically, the Study team will isolate CSCs from whole blood then
direct them down an EC pathway. Once differentiated the study team will characterize their
phenotype.
Specific Aim #2: Culture mature ECs, SMCs, and CSC derived ECs under conditions of low Earth
orbit (LEO) aboard the ISS. Specifically, The study team will use advanced flight hardware to
establish an active cell culture on the ISS. The cells will be cultured for a duration of 3
and 10 days, at which time the cells will be frozen for subsequent analysis. Simultaneously,
the study team will culture the same populations in a ground based microgravity simulator as
well as a normal gravity control.
Specific Aim #3: Assess the morphologic and genetic changes in cells after 3 and 10 days of
space flight. Specifically, upon return to Earth, a transcriptome analysis will be completed
from the frozen cell samples to assess changes in the cells molecular machinery.
This proposed study builds upon the abundant literature, including our own, surrounding the
effects of ground based simulated microgravity on vascular endothelial cells. However, the
study team include the less studied populations of smooth muscle cells and stem cell derived
ECs. The goal of this work is to leverage conditions on the ISS, a powerful one-of-a-kind
microgravity research platform in low Earth orbit, to study these cells and their cellular
processes as it relates to cardiovascular disease (CVD) and cardiovascular deconditioning.
This work seeks to reveal currently unknown changes in vascular cell health that lead to
these diseases. The impact of this work is broad and can lead to new treatment options for
millions of people who suffer from CVD including neointimal hyperplasia.
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