Martinez Luna, C. | Search bioRxiv

bioRxiv2026

Microgravity enhances the viability of midbrain organoids on the International Space Station.

As human spaceflight becomes increasingly relevant, understanding how microgravity affects the human brain is an important but largely unexplored question, particularly in the context of neuronal function and vulnerability to neurodegeneration. Direct investigation of these processes in humans is not feasible, necessitating the use of physiologically relevant in vitro model systems. Three-dimensional human brain organoids recapitulate key aspects of brain development and organization and provide an experimentally accessible platform to study neuronal responses under controlled conditions. Here, within the framework of the student competition "Uberflieger 2", we investigated the effects of long-term microgravity on human midbrain organoids cultured for 40 days aboard the International Space Station (ISS). Midbrain organoids reproduce essential features of dopaminergic neuron development and are widely used to model Parkinsons disease and related neurodegenerative processes. To enable spaceflight experiments, we developed and implemented an autonomous culture system adapted to the constraints of the ISS environment. During the mission, a hardware malfunction impaired scheduled medium exchange, introducing an additional metabolic stress condition. Despite these limitations, ISS-cultured organoids remained viable and showed robust neurite outgrowth. Molecular and imaging analyses revealed that exposure to microgravity in combination with nutrient limitation induced a coordinated response involving cytoskeletal remodeling, neuronal plasticity, and selective vulnerability of dopaminergic neurons. These findings demonstrate that human midbrain organoids can maintain key structural and functional properties under prolonged spaceflight-associated stress while activating adaptive response programs. This work highlights the potential of organoid-based systems to investigate neurobiological effects of microgravity and provides a foundation for future studies addressing mechanisms relevant to neurodegenerative disease.

neuroscience↗

bioRxiv2025

CIT tumor lines: A novel series of immunogenic squamous cell skin carcinoma cell lines derived from chemical carcinogenesis

Immunotherapy is now widely used to treat advanced-stage skin cancer, but it is effective for only approximately half of skin cancer patients, including both patients with melanoma and cutaneous squamous cell carcinoma (cSCC). To overcome current barriers, preclinical mouse models that faithfully recapitulate the tumor genetics, mutation burdens, and neoantigen patterns of specific human tumor types are essential. However, while many models exist for melanoma, there are currently relatively few transplantable murine models of cSCC, which is responsible for nearly as many deaths as melanoma each year. Here we describe a novel series of 11 cSCC tumor lines, the Carcinogen-Induced Tumor (CIT) lines, syngeneic to the FVB strain, that address this need. The CIT lines were established from skin carcinomas induced by DMBA and TPA treatment and harbor genetic drivers and overall tumor mutational burdens that recapitulate those found in cSCC. Each CIT line gives rise to tumors with a consistent immune infiltration pattern, ranging from T cell-rich "hot" tumors to T cell-poor "cold" tumors. Hot CIT lines exhibit partial responses to treatment with immune checkpoint inhibitors, and we have identified two neoantigens present in an immunotherapy-responsive CIT line. The CIT lines thus provide a valuable new series of preclinical models for studying anti-tumor immune responses and developing strategies to improve immunotherapy efficacy in cSCC.

cancer biology↗