Cultures Through Time: Forging a Xeno-Free Future for Cell Culture-Based Virology

As a cornerstone of modern science, cell lines are the foundational platforms for key medical advances. They enable vaccinology (by propagating and attenuating viruses), gene therapy (by facilitating vector development), and biopharmaceutical production (through recombinant protein expression). Mammalian, avian, and insect cell expression systems like Vero, MDCK, HEK293, BHK21, CHO,PER.C6, EB66, are indispensable cellular platforms that produce enhanced biologic yields and quality biotherapeutics suited to regulatory and industrial requirements. Simultaneously, advances in cell biology ranging from engineering and optimization of cell culture media to designer cell lines, have enabled improved scalability, genetic stability, and biosafety of the end-product biologic. A critical shift is underway from serum-dependent media to serum-free, chemically defined, and xeno-free alternatives, which minimize culture media variability, reduce exogenous contamination risks, and align with Good Manufacturing Practice standards. This review emphasizes the far-reaching influence of cell culture systems as the expression powerhouse that sustains modern virology whilst focusing on recent cell-engineering methods and optimization strategies in culture media that facilitated this shift.