International Space Station National Laboratory Research Articles

Effects of dexamethasone and IGF-1 on post-traumatic osteoarthritis-like catabolic changes in a human cartilage-bone-synovium microphysiological system in space and ground control tissues on earth

Post-traumatic Osteoarthritis (PTOA) results from traumatic joint injuries (such as an ACL rupture). Mechanical impact and an immediate synovial inflammatory response can result in joint tissue degradation and longer-term progression to PTOA. Astronauts are susceptible to increased exercise-related joint injuries leading to altered musculoskeletal physiology, further escalated due to microgravity and increased exposure to ionizing radiation. We applied a human Cartilage-Bone-Synovium (CBS) coculture model to test the potential of low-dose dexamethasone (Dex) and IGF-1 in ameliorating PTOA-like degeneration on Earth and the International Space Station-National Laboratory (ISS-NL, ISS for short). CBS cocultures were established using osteochondral plugs (CB) subjected to compressive impact injury (INJ) followed by coculture with synovium (S) explants. Study groups consisted of control (CB); disease [CBS + INJ]; treatment [CBS + INJ + Dex + IGF-1]; and drug-safety [CB + Dex + IGF-1]. Outcome measures included cell viability, altered matrix glycosaminoglycans (GAG) and collagens, multiplex-ELISA quantification of released cytokines, histopathology, and metabolomic and proteomic analyses of spent media. A 21-day study on ISS-NL explored PTOA-like pathogenesis and treatment in microgravity. Tissue cards for study groups were cultured in custom-built culture chambers within multi-use variable-g platforms (MVPs). A marked upregulation in the release of inflammatory cytokines and tissue-GAG loss was observed in CBS + INJ groups in space and ground controls utilizing tissues from the same donors, similar to that reported in a previous multi-donor study on Earth; these changes were partly ameliorated by Dex + IGF-1, but with donor variability. Metabolomic and proteomic analyses revealed an array of distinct differences between metabolites/proteins released to the medium in Space versus on Earth.

Intellectual property rights in outer space: How can pharmaceutical companies protect COVID‐19 vaccine and immunotherapy developments aboard the ISS US national laboratory?

AbstractBelieving that space pharmaceuticals might be the key to winning the battle against COVID‐19, global pharmaceutical companies such as AstraZeneca and Sanofi Pasteur are currently collaborating with the International Space Station National Laboratory (ISS‐NL) on research projects aiming to develop vaccine‐and‐immunotherapy products. The present legal regime for outer space, however, does not provide clear guidelines on safeguarding intellectual property rights (IPRs), due to the difficulties of reconciling the territorial nature of patent law and the nonterritorial nature of space law. Responding to such a legal gap, this research paper argues how pharmaceutical companies can protect such medical innovations by taking into consideration the international principles of space law addressing IPRs and extraterrestrial jurisdiction, as well as the legal regime of the ISS‐NL. With the exception of the possibility of the barriers between the two areas of law not being insurmountable, the proposed COVID‐19 TRIPS Waiver furthermore impacts space pharmaceuticals' IPRs and commercialization, which leads to the identification of some advantageous forms of agreements, including the Joint Endeavor Agreement, the Space Act Agreement, as well as the Cooperative Research and Development Agreement, for pharmaceutical companies defined as agreement partners with the National Aeronautics and Space Administration.

Tissue Chips in Space: Modeling Human Diseases in Microgravity.

Microphysiological systems (MPS), also known as "organs-on-chips" or "tissue chips," leverage recent advances in cell biology, tissue engineering, and microfabrication to create in vitro models of human organs and tissues. These systems offer promising solutions for modeling human physiology and disease in vitro and have multiple applications in areas where traditional cell culture and animal models fall short. Recently, the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH) and the International Space Station (ISS) U.S. National Laboratory have coordinated efforts to facilitate the launch and use of these MPS platforms onboard the ISS. Here, we provide an introduction to the NIH Tissue Chips in Space initiative and an overview of the coordinated efforts between NIH and the ISS National Laboratory. We also highlight the current progress in addressing the scientific and technical challenges encountered in the development of these ambitious projects. Finally, we describe the potential impact of the Tissue Chips in Space program for the MPS field as well as the wider biomedical and health research communities.

Human cartilage-bone-synovium microphysiological system to study ptoa pathogenesis and treatment on earth and in space

Purpose: Acute joint injuries from sports, exercise or accident-related trauma often progress to post-traumatic Osteoarthritis (PTOA), comprising ∼12% of all OA cases. Such joint injuries can cause mechanical damage to cartilage combined with an inflammatory response associated with the synovial lining of the joint capsule. Together, these events lead to cartilage and subchondral bone pathologies including cell death, tissue degradation, neoangiogenesis, osteophyte and cyst formation and synovial fibrosis. Astronauts on International Space Station-National Laboratory (ISS-NL) sustain a higher rate of exercise-related injuries, including those compromising joints, during their training and mission period. Acknowledging the urgent need to identify disease-modifying therapeutics to ameliorate degenerative evolution of OA/PTOA, we carried out this study to (1) simulate aspects of acute joint injury biology on earth and in space using a human Cartilage-Bone-Synovium coculture model (CBS-MPS), (2) to investigate the potential of dexamethasone (Dex) in reducing cell death and ECM degradation, and (3) to utilize a Multi-Use Variable-g Platform (MVP) to study PTOA-related pathogenesis and management on the ISS. Methods: Osteochondral plugs (3.5mm diameter and 5mm thick, including 1.5-2mm thick cartilage) harvested from condyles and trochlear grooves of cadaveric human distal femurs (n=8 knees, Collins grade 1/2, 64-82 yr) were co-cultured with 4-5mm diameter synovium explants harvested from synovial joint capsule of the same knees. All procedures were approved by the Rush University Medical Center Institutional Review Board and the Committee on the use of Humans as Experimental Subjects at MIT. PTOA-like mechanical trauma was simulated by subjecting the cartilage surface of the osteochondral plugs to a single injurious unconfined compression of 60% strain rate to a peak stress of 5MPa using an incubator-housed loading apparatus. The study design included the following groups: (1) Mechanical injury (INJ) - injured osteochondral plugs were cultured in presence of pro-inflammatory cytokines (including TNF-α, IL-6 and IL-8) that were released by synovial explants and quantified by multiplex-readout in situ, (2) Treatment group (INJ + DEX): 100nM Dex was added to the cocultures of injured osteochondral plugs and synovial tissues immediately after injury. A preliminary science validation test was performed to identify a suitable mechanism to adapt CBS cocultures to the custom experiment module and the MVP facility. Engineering validation testing was then carried out to build logistical protocols for the spaceflight including transport of cultures and simulation of tasks preceding launch operations. Results: The levels of pro-inflammatory cytokines such as IL-6, IL-8 and TNF-α were upregulated in CBS cocultures. The combination of mechanical injury and increased release of inflammatory cytokines from synovial tissues caused extensive cell death and biochemical changes in both bone and cartilage. In the INJ group, cartilage tissue showed widespread cell death [Fig1 a], and subchondral bone showed increased cell death as well, indicated by numerous empty lacunae in the matrix. Biochemical analysis showed aggravated release of matrix component (including GAGs) into the medium, associated with cartilage degradation [Fig 1c]. Addition of Dex significantly reduced the injury-induced cell death [Fig 1b] and GAG loss by week 2 [Fig 1c]. For spaceflight preparation, tissue cards [Fig 1d] were optimized for long-term holding and maintenance of CBS co-cultures, which were placed into custom culture chambers [Fig 1e]. Multiple tests using this instrumentation were used to guide the design and operation of automated MVP facility [Fig 1f]. Investigation of disease biology and acute injury management is currently being tested in preparation for eventual spaceflight experiments in microgravity aboard ISS-NL. Conclusions: By providing a platform to study cartilage, bone and synovium together, our CBS MPS can potentially enable a more physiologically relevant understanding of tissue interactions that may lead to PTOA pathogenesis. This system can also be used to test the efficacy of therapeutics. In Space, this MPS will be used to explore the role of therapeutic agents to ameliorate cartilage degradation in microgravity to support astronaut health during long space missions.