Award Abstract # 1929028
ISS: Microphysiologic Model of Human Cardiovascular Stiffness-Related Diseases in Microgravity

NSF Org: CMMI
Division of Civil, Mechanical, and Manufacturing Innovation
Recipient: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Initial Amendment Date: July 29, 2019
Latest Amendment Date: June 26, 2023
Award Number: 1929028
Award Instrument: Standard Grant
Program Manager: Shivani Sharma
shisharm@nsf.gov
 (703)292-4204
CMMI
 Division of Civil, Mechanical, and Manufacturing Innovation
ENG
 Directorate for Engineering
Start Date: September 1, 2019
End Date: August 31, 2024 (Estimated)
Total Intended Award Amount: $499,879.00
Total Awarded Amount to Date: $515,832.00
Funds Obligated to Date: FY 2019 = $499,879.00
FY 2023 = $15,953.00
History of Investigator:
  • Kevin Costa (Principal Investigator)
    kevin.costa@mssm.edu
  • David Sachs (Co-Principal Investigator)
Recipient Sponsored Research Office: Icahn School of Medicine at Mount Sinai
1 GUSTAVE L LEVY PL
NEW YORK
NY  US  10029-6504
(212)824-8300
Sponsor Congressional District: 13
Primary Place of Performance: Icahn School of Medicine at Mount Sinai
One Gustave L. Levy, Box 1075
New York
NY  US  10029-6574
Primary Place of Performance
Congressional District:
13
Unique Entity Identifier (UEI): C8H9CNG1VBD9
Parent UEI: C8H9CNG1VBD9
NSF Program(s): Special Initiatives,
Engineering of Biomed Systems,
BMMB-Biomech & Mechanobiology
Primary Program Source: 01002324DB NSF RESEARCH & RELATED ACTIVIT
01001920DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 070Z, 116E, 9178, 9231, 9251
Program Element Code(s): 164200, 534500, 747900
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

Cardiovascular disease is one of the most devastating health problems in the modern world, with heart failure and hypertension impacting a rising percentage of the aging population. Increased cardiovascular cell and tissue stiffness is a characteristic associated with normal aging as well as a wide range of cardiovascular diseases. Interestingly, astronauts exposed to microgravity also experience aortic stiffening and reduced cardiac function. Thus, understanding the process and cardiac consequences of arterial stiffening in microgravity may provide new insights into the related cardiovascular diseases associated with aging on Earth. This may then lead to new ways to improve cardiovascular health for humans on Earth as well as for astronauts in microgravity. The overall objective of this research project is to utilize organ-on-chip technology to study accelerated cardiovascular aging in microgravity. The researchers will deploy a novel, organ-on-chip model, known as a micro-CVchips, of the human cardiovascular system in which cardiac and arterial structures will be grown from human pluripotent stem cells and linked in a functional, miniature circulatory system. This will allow for the modeling of fluid movement and organoid stiffness in addition to cell and tissue physiology. A set of these micro-CVchips will be sent to the International Space Station (ISS) to experience microgravity, where they will be monitored and manipulated within a robotic laboratory to determine any signs of an accelerated aging process. Finally, the micro-CVchips will be retrieved and examined on Earth with a set of thorough biological tests. These chips will be compared to control chips that remained on Earth, in addition to patient samples obtained from a tissue biobank at Mount Sinai. This project will also be used as a vehicle to teach and inspire local high school students as part of an ongoing collaboration between Mount Sinai and several New York City schools.

This project is supported by 3 scientific objectives. First, a multi-tissue in vitro microfluidic human organoid model of the cardiovascular system will be characterized. This microfluidic system includes separate cardiac and arterial organoid compartments linked in an endothelialized circulatory system. It will be capable of autonomous cardiac driven flow and arterial driven fluidic resistance changes, allowing it to model arterial stiffening and associated cardiac diastolic dysfunction. Second, a set of the micro-CVchips will be sent to the ISS to experience extended microgravity. Tests for phenotype markers of arterial stiffening and diastolic cardiac dysfunction will be made on board the ISS using an innovative robotic pressure control and video system for near-real-time terrestrial monitoring. This will be combined with post-flight histology studies. Finally, the post-flight analysis of the samples returned from the ISS will be compared to control samples maintained on Earth through numerous molecular biology techniques in order to identify novel disease biomarkers and pathways. The data from the micro-CVchip will also be compared to data obtained from patient samples obtained through the Mount Sinai Cardiovascular Biorepository and 'Omics Facility in order to evaluate the strengths and limitations of the new in vitro model of cardiovascular aging.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Please report errors in award information by writing to: awardsearch@nsf.gov.

Print this page

Back to Top of page