Introduction

Microgravity, the condition of near-weightlessness experienced during spaceflight, fundamentally alters the mechanical forces that govern cellular structure and function. This comprehensive review synthesizes a wide body of research to provide a detailed overview of how human and animal cells respond to this unique environment. The paper explores the profound effects of microgravity on key biological systems, highlighting the dual implications for astronaut health during long-duration missions and for advancing biomedical applications on Earth.

Research Objective

This review aimed to consolidate and analyze recent scientific literature on the cellular and molecular impacts of microgravity. The primary goals were to:

  • Summarize the effects of microgravity on critical physiological systems, including the immune, musculoskeletal, cardiovascular, and metabolic systems.
  • Elucidate the molecular pathways (e.g., PI3K-Akt, Hippo, NF-κB) that are disrupted or activated by the absence of gravity.
  • Evaluate the potential of microgravity as a tool for advancing research in cancer biology, tissue regeneration, and stem cell therapies.

Key Findings

  • Profound Immune System Dysfunction: Microgravity significantly suppresses T-cell activation and proliferation, impairs the differentiation of hematopoietic stem cells into macrophages, and reduces the cytotoxic activity of Natural Killer (NK) cells, leading to a compromised immune response.
  • Enhanced Cardiomyocyte Maturation: Paradoxically, simulated microgravity improves the maturation of cardiomyocytes derived from human pluripotent stem cells. This includes enhanced mitochondrial biogenesis, improved calcium handling, and advanced structural development (e.g., increased sarcomere length), making them more suitable for regenerative therapies.
  • Accelerated Bone and Vascular Degradation: Microgravity disrupts mechanotransduction in osteoblasts, leading to accelerated bone mass loss. In endothelial cells, it causes a 30% reduction in cell stiffness after 24 hours, cytoskeletal reorganization, and inhibited proliferation, which can impair vascular integrity.
  • Altered Cancer Cell Dynamics: In microgravity, many cancer cell lines (e.g., thyroid, breast) spontaneously form 3D multicellular spheroids that better mimic in-vivo tumors, creating superior models for oncology research. It can also induce apoptosis (programmed cell death) and reduce the malignant phenotype in certain cancer cells.
  • Metabolic and Gut Dysregulation: In primate models, simulated microgravity induces hepatic lipotoxicity (fat accumulation in the liver) and is linked to intestinal dysbiosis and endotoxemia, highlighting systemic metabolic risks.
  • Boosted Stem Cell Differentiation: Microgravity enhances the differentiation of human pluripotent stem cells into hematopoietic lineages by activating the PI3K-Akt pathway, which promotes cell survival and proliferation.

Methodology

This publication is a comprehensive literature review, not a single experiment. The authors conducted a systematic search of the PubMed, Scopus, and Embase databases to synthesize findings from a wide range of studies, including:

  • Organisms Studied: Research on human cells, mice, rhesus macaques, and various in-vitro cell cultures (e.g., stem cells, cancer cells, endothelial cells).
  • Experimental Conditions: The review covers data from both true spaceflight experiments aboard the International Space Station (ISS) and ground-based simulated microgravity using devices like Random Positioning Machines (RPMs) and rotating bioreactors.
  • Techniques Analyzed: The findings are based on transcriptomics (RNA-seq), proteomics, advanced microscopy, and functional cellular assays.

Importance for Space Missions

The findings summarized in this review are critical for long-duration space exploration, such as missions to Mars. The documented immune suppression, bone density loss, and metabolic disturbances represent major health risks that require effective countermeasures. Understanding the underlying cellular mechanisms, such as the disruption of the RAS/ERK/NF-κB pathways, is the first step toward developing targeted therapies. Furthermore, the discovery that microgravity can enhance the maturation of cardiomyocytes and other tissues opens the possibility of using the space environment for on-demand tissue engineering to treat astronaut health issues during missions.

Knowledge Gaps & Future Research

While our understanding of cellular responses to microgravity has grown, significant questions remain:

  • Do the effects observed in short-term spaceflight or simulations persist or worsen during multi-year missions?
  • How accurately do ground-based simulators replicate the complex environment of space, which includes radiation alongside microgravity?
  • Can we develop specific pharmaceutical or mechanical interventions to counteract the negative effects on the immune and musculoskeletal systems by targeting the identified molecular pathways?
  • What are the precise mechanisms that allow microgravity to enhance the maturation of some stem cell lineages while inhibiting others?

Results

This review confirms that microgravity is a powerful biological effector, acting as both a physiological stressor and a unique research tool. For space exploration, its detrimental effects on the immune, musculoskeletal, and metabolic systems pose significant challenges to maintaining crew health. For terrestrial medicine, its ability to promote 3D tissue formation and enhance stem cell maturation offers transformative potential for regenerative medicine, drug discovery, and cancer research. Continued investigation into these cellular phenomena is essential for enabling humanity’s future in space and advancing human health on Earth.

Data Visualization