• 3D Cellular Models and Human Organoids: Bridging Genetic Research and Precision Medicine
  • Mahoora Rahimi,1,* Nadiya Rahimi,2
    1. Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
    2. Department of Biomedical Engineering, Faculty of Electrical Engineering and Biomedical Engineering, Sadjad University, Mashhad, Iran


  • Introduction: The modeling of genetic disorders remains a significant challenge in biomedical engineering and medical genetics. Conventional two-dimensional (2D) cultures and animal models often do not replicate the structural and functional intricacies of human tissues, resulting in limited translational significance. Recent advancements in human organoids and three-dimensional (3D) cellular models have established transformational platforms that more precisely replicate human physiology in vitro. These technologies, especially when integrated with induced pluripotent stem cells (iPSCs) and CRISPR-Cas9 gene editing, offer unparalleled prospects for elucidating disease causes, enhancing drug development, and advancing personalized medicine. Organoids and 3D models enable the examination of patient-specific genetic variations in physiologically relevant systems, marking a paradigm shift in precision healthcare.
  • Methods: This research used a narrative review method for the literature. Databases such as PubMed, Scopus, and Web of Science were queried for publications published in the last decade, using keywords including "human organoids," "3D cellular models," "genetic disorders," "CRISPR-Cas9," "induced pluripotent stem cells (iPSCs)," "personalized medicine," and "biomedical engineering." Studies were selected for their relevance to disease modeling, pharmacological development, regenerative medicine, and clinical applications. Review papers, experimental reports, and case studies were assessed to include both the scope and intricacies of the topic.
  • Results: Research repeatedly shows that organoids produced from iPSCs or adult stem cells can more accurately imitate the architecture, cellular diversity, and functioning of genuine tissues compared to 2D cultures. Brain organoids demonstrate neuronal connection and electrophysiological activity, providing effective models for neurodevelopmental and neurodegenerative illnesses, including autism spectrum disorders, microcephaly, and Alzheimer’s disease. Intestinal and pulmonary organoids derived from cystic fibrosis patients have elucidated disease pathogenesis and facilitated individualized pharmacological testing. Three-dimensional cellular models enhance organoid systems by replicating tissue microenvironments, including extracellular matrix characteristics and intercellular interactions. These models have demonstrated efficacy in replicating tumor microenvironments, thereby enabling investigations into metastasis and the development of drug resistance. The use of CRISPR-Cas9 has significantly enhanced the accuracy of these systems, enabling the targeted introduction or correction of mutations associated with conditions such as muscular dystrophy, Huntington’s disease, and other cardiomyopathies. Drug development constitutes a significant translational application. Organoid-based screening has surpassed conventional approaches in forecasting patient-specific medication responses, especially in cancer. Research using colorectal cancer organoids has effectively informed chemotherapy selection in clinical environments, underscoring their significance in enhancing customized treatment approaches. In addition to oncology, high-throughput screening technologies combined with organoid cultures are facilitating the discovery of efficacious drugs with enhanced safety profiles. Notable emerging applications exist in tissue engineering and regenerative medicine. Progress in vascularized and multicellular organoid systems is approaching the development of functioning tissue structures suitable for transplantation. This advancement facilitates the resolution of the donor organ scarcity and the investigation of personalized regenerative treatments.
  • Conclusion: Human organoids and three-dimensional cellular models represent a crucial leap in biomedical engineering, providing physiologically relevant systems for modeling genetic disorders and accelerating the shift toward personalized therapy. Their capacity to capture patient-specific genetic variation facilitates the development of customized therapy methods, enhances drug screening accuracy, and enables novel methodologies in regenerative medicine. Nonetheless, significant obstacles persist. The standardization of methods, integration of multicellular and immunological elements, scalability for clinical application, and ethical issues related to iPSCs and genome editing need meticulous study. Resolving these difficulties will be crucial for realizing the full translational potential of these technologies. With advancements in the discipline, organoids and 3D models are expected to play a pivotal role in precision healthcare, bridging the gap between basic research and clinical practice. By incorporating omics technology, gene editing instruments, and bioengineering methodologies, these models enhance our understanding of genetic disorders and move us closer to a future where medical treatments are tailored to the distinct genetic profiles of individual patients. The integration of these technologies highlights a breakthrough period in medical genetics and biomedical engineering, significantly impacting patient care globally.
  • Keywords: Human Organoids, 3D Cellular Models, Genetic Diseases, Personalized Medicine, CRISPR-Cas9