ISS: Microgravity-altered stem cell vascularization and extracellular vesicle production: Implications for Heart and Skin Nanomedicines

Aging and vascular disease can result in negative changes to blood vessels, called vascular remodeling. Exposure to microgravity during spaceflight alters fluid flow in organs throughout the body leading to adaptations in blood vessel thickness. This vascular remodeling may mimic what occurs during disease and aging.

Identifying strategies to prevent or reverse this vascular remodeling will not only protect astronauts in deep space but promises to improve vascular health on Earth. The planned approach is to grow three-dimensional tissue or “organoids” from heart and skin cells in a porous material called a Bio-block that mimics the cells’ natural environment.

Bio-Blocks can be designed with different stiffnesses and protein coatings to support the formation of blood vessel-like microchannels around the organoids to simulate vascularization. These heart and skin surrogates serve as a cell culture platform to study the effects of microgravity and radiation on heart and skin vascular behavior. Our team will also collect organoid-secreted particles called extracellular vesicles.

Cells release extracellular vesicles to communicate with other cells and send cues to form new blood vessels. These vesicles may assemble better in microgravity. Our project will provide a proof of concept to test if these bioproducts can be used for clinical research.

Bio-Blocks may serve as an in-space cell bioreactor to improve the organoid model and extracellular vesicle production. The partnership formed by Micro-gRx, the University of Florida, Ronawk, and Redwire seeks to advance tissue engineering and in-space cell tools that benefit life on Earth and will engage students in cross-disciplinary team-based learning at the interface of biomedical engineering, pharmacy, and aerospace technologies.

The Micro-gRx-University of Florida partnership aims to advance in-space cell therapy tools for regenerative medicine by advancing dynamic three-dimensional culture processes. The team will use tissue mimetic structures called Bio-Blocks (Ronawk) custom designed and coated with endothelial cells to create a vascular scaffold and cell bioreactor for cardiac and skin stem cell derived organoid cultures.

Endothelial cells are sensitive to alterations in flow-mediated shear stress and blood flow forces are altered in spaceflight. The customized Bio-Blocks for vascularized organoid culture (Bio-VOC) will serve as a model to elucidate mechanotransduction pathways induced by altered hemodynamics. The rationale is that the pro-angiogenic Bio-VOCs will support endothelial tubular structures, thereby releasing bioactive signaling cues that will promote our understanding of how blood flow alterations activate different inflammatory responses in vascularized systems.

The planned work seeks to evaluate the biomanufacturing of potential high-value extracellular vesicles (EVs). Stem cell secreted EVs hold therapeutic potential due to cell-to-cell communication with endothelial cells and promotion of vascular remodeling. The aims are to grow cardiac and epidermal organoids within the vascularized perfusable channels of the Bio-VOCs and characterize secreted EVs for their angiogenic potential.

The project will use Redwire’s Multi-use Variable-gravity Platform (MVP). Four MVPs will be seeded with 72 Bio-VOCs. Elucidating the mechanisms that altered hemodynamics plays in microgravity which may mimic what occurs during disease or aging and developed countermeasures will not only protect astronauts in deep space but promises to improve vascular health on Earth.

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.