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The intestine is an essential digestive organ and is recognized as one of the most structurally complex organs in the human body. It participates in nutrient metabolism, immune regulation, and mucosal barrier maintenance to sustain physiological homeostasis. Intestinal epithelial injury, immune activation, and gut microbiota dysbiosis collectively promote the occurrence and progression of intestinal diseases. Traditional studies on intestinal diseases mainly rely on cell lines and animal models, both of which have obvious limitations. Conventional cell lines lack cell–cell and cell–matrix interactions in the intestinal microenvironment and cannot faithfully recapitulate the genetic characteristics of patients. Animal experiments are limited by high costs, long experimental cycles, and unavoidable species differences between humans and rodents. In 2009, the Hans Clevers team first established intestinal organoids using mouse Lgr5-positive intestinal stem cells. Organoid technology was selected as one of the top ten breakthrough technologies by Science in 2013 and was named the Method of the Year by Nature in 2017. Characterized by human origin and high physiological similarity, organoids can faithfully recapitulate multiple organ-specific disease phenotypes in vitro, including tumors, primary sclerosing cholangitis, and inflammatory bowel disease (IBD). Organoid-based mechanistic exploration, therapeutic evaluation, and off-target effect detection effectively reduce the failure rate of clinical drug development. Meanwhile, organoids exhibit great application potential and commercial value for precision medicine and individualized clinical medication guidance. Intestinal organoids are derived from Lgr5-enriched stem cells located at the crypt base and exhibit typical three-dimensional structures with inward lumens and apical surfaces facing the extracellular matrix. Intestinal organoids contain all major differentiated intestinal cell types, including Paneth cells, absorptive enterocytes, colonocytes, goblet cells, and enteroendocrine cells. They recapitulate the cellular composition and biological characteristics of the intestinal epithelium, possess self-renewal capacity, and maintain physiological functions such as water and ion absorption and substance transport. Furthermore, intestinal organoids retain the individual genetic background of donors, showing unique advantages over conventional cell lines and animal models.

Brain organoids recapitulate multiple key features of embryonic cortical development and can differentiate into diverse cell types corresponding to distinct brain regional lineages. For example, brain organoids simultaneously generate dorsal and ventral forebrain progenitors, which further differentiate into excitatory neurons and inhibitory interneurons respectively. In addition, patient-derived human induced pluripotent stem cells (hiPSCs) can be used to establish disease-specific brain organoid models for functional genomic research on neurological disorders such as microcephaly and autism. Accordingly, brain organoids serve as an ideal experimental system for investigating how disease-associated genes regulate human brain development. This system enables visual analysis of the migratory behavior of human cortical interneurons. It greatly improves the model complexity and physiological resemblance for developmental cell biology research on human neurological diseases, and provides a brand-new platform for disease mechanism exploration and drug screening.

The liver is a structurally intricate and functionally indispensable human organ, serving as a core hub for systemic metabolism, detoxification, protein synthesis, digestion, nutrient storage, and bile secretion. Owing to its versatile and sophisticated physiological functions, hepatic damage frequently triggers a cascade of intricate clinical complications. A spectrum of liver disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver cirrhosis, and hepatocellular carcinoma, is associated with high mortality and constitutes a critical global public health challenge. Current studies exploring the pathogenic mechanisms of liver diseases, drug toxicological assessment, and therapeutic innovation predominantly depend on conventional cell and animal models. Despite their widespread application in basic hepatic research, these experimental systems have inherent deficiencies and cannot faithfully replicate the elaborate structural architectures and physiological properties of the human liver. As an innovative and powerful research platform, organoids are self-assembled constructs generated from adult stem cells, pluripotent stem cells, or tissue progenitors, which closely recapitulate the structural integrity and functional signatures of native organs. Combining unique strengths such as high-throughput screening feasibility, facile genetic modification, and superior physiological mimicry, organoid models have been extensively adopted in multiple biomedical research domains.

The human lung represents a functionally essential and structurally sophisticated organ composed of over 40 distinct cell types, predominantly including epithelial cells, immune cells, endothelial cells, and stromal cells. As a vital organ continuously exposed to airborne pollutants, cigarette smoke, pathogenic bacteria, viruses, and various toxic stimuli, the lung is highly susceptible to persistent tissue injury, which ultimately drives the progression of multiple pulmonary disorders, such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and diverse respiratory infections. Immortalized cell lines and primary human lung cells have long served as conventional research models for investigating lung development and disease pathogenesis due to their accessibility and low experimental cost. However, primary cells exhibit restricted proliferation and passaging ability, limiting their application in long-term experimental studies, whereas immortalized cell lines display significant genetic and phenotypic deviations from authentic in vivo lung tissues. In addition, animal models are hampered by inherent interspecies differences and fail to recapitulate the intricate cellular heterogeneity of the human lung, resulting in unavoidable experimental limitations. Possessing robust self-renewal capacity and multilineage differentiation potential, lung organoids have emerged as an advanced and versatile model for elucidating the molecular mechanisms underlying smoking-related pulmonary diseases and facilitating therapeutic screening. Accumulating evidence has confirmed that lung organoids faithfully recapitulate human lung developmental processes, three-dimensional tissue architecture, and physiological functions. Accordingly, they provide a powerful experimental platform for exploring lung development, injury repair, and pathological mechanisms, holding great promise for broad biomedical applications.