iPSC-derived and Patient-Derived Organoids: Applications and challenges in scalability and reproducibility as pre-clinical models

Abstract

Recent advancements in stem cell technology have led to the development of organoids – three-dimensional (3D) cell cultures that closely mimic the structural and functional characteristics of human organs. These organoids represent a significant improvement over traditional two-dimensional (2D) cell cultures by preserving native tissue architecture and cellular interactions critical for physiological relevance.

This review provides a comprehensive comparison between two main types of organoids: induced Pluripotent Stem Cell (iPSC)-derived and Adult Stem Cell (ASC)-derived (also known as Patient-Derived Organoids, PDOs). iPSC-derived organoids, derived from reprogrammed cells, exhibit remarkable plasticity, and can model a wide range of tissues and developmental stages. They are particularly valuable for studying early human development, genetic disorders, and complex diseases. However, challenges such as prolonged differentiation protocols and variability in maturation levels remain significant hurdles. In contrast, ASC-derived organoids, generated directly from patient tissues, faithfully recapitulate tissue-specific characteristics and disease phenotypes. This fidelity makes them indispensable for personalized medicine applications, including drug screening, disease modeling, and understanding individualized treatment responses.

The review highlights the unique advantages and limitations of each organoid type, emphasizing their roles in advancing biomedical research and drug discovery. It addresses key challenges in organoid technology, such as scalability, reproducibility, and the need for standardized culture protocols. Furthermore, it explores recent innovations in scaffold-guided organoid engineering and the integration of organoids with advanced technologies like artificial intelligence and high-throughput screening.

The integration of organoids with cutting-edge technologies holds promise for enhancing their utility in modeling complex human diseases and accelerating drug discovery and development. By providing more physiologically relevant models of human organs, organoid technology is poised to revolutionize biomedical research, offering new insights into disease mechanisms and personalized therapeutic strategies.