Advances in marine invertebrate cell culture: historical progress, persistent challenges, and emerging biotechnological prospects

Marine invertebrates represent one of the most diverse and underexploited reservoirs of novel bioactive compounds and models for regenerative biology, yet their full potential remains limited by the absence of established cell lines. Despite over six decades of research, no continuous, immortalized cell lines were available from any marine invertebrate species until recent breakthroughs in embryonic cultures. This comprehensive review synthesizes historical and contemporary advancements in primary cell culture across major phyla, including Porifera, Cnidaria, Mollusca, Crustacea, Echinodermata, and others, with a focused examination of methodological innovations since 2015. Key discussions encompass refined isolation techniques, tailored media compositions, the incorporation of omics-driven insights, ongoing hurdles such as rapid cellular quiescence and contamination issues, and promising applications in pharmaceutical discovery, aquaculture disease management, and ecotoxicology. By identifying four pivotal knowledge gaps—ranging from media optimization to stemness maintenance—we propose multifaceted strategies that integrate multi-omics analyses, CRISPR-based genetic manipulations, and global collaborative frameworks to facilitate the development of stable, long-term marine invertebrate cell lines, thereby unlocking sustainable biotechnological opportunities.