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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.

Blood glucose homeostasis in the human body is dynamically regulated by insulin secreted from the pancreatic islets of Langerhans, which can sensitively detect fluctuations in circulating glucose concentrations. Permanent damage to this homeostatic regulatory mechanism triggers diabetes mellitus, which has gradually become a major threat to global public health. Epidemiological data predict that the number of adult diabetic patients will rise to 578 million by 2030 and further increase to 700 million by 2045. Conventional in vitro cell culture systems remain the primary approach to investigate the biological characteristics of pancreatic cells. Nevertheless, these systems fail to reconstruct the complex microenvironmental conditions within living human tissues. In recent years, considerable progress has been made in tissue engineering. Researchers have constructed organoids by utilizing the innate self-assembly capacity of mammalian cells. Generated via advanced three-dimensional culture technology, organoids can closely mimic the unique structural features and functional phenotypes of native human organs. Within pancreatic organoids, multiple cell types engage in dynamic interactions through sophisticated signal communication, mutual regulation, inductive feedback and functional coordination, collectively facilitating the formation of miniature tissue units with mature physiological functions. Organoids can effectively simulate the structure and function of human tissues in vitro. Accordingly, islet organoids offer a promising experimental platform for diabetic pathological modeling, candidate drug screening, and the functional quality assessment of cell-based therapies for diabetes. Diverse applications of pancreatic organoids. Pancreatic organoids recapitulating both exocrine and endocrine compartments of the pancreas are predominantly generated from human pluripotent stem cells (hPSCs) and clinical primary adult stem cells (ASCs). Organoid technology enables the establishment of ideal in vitro models that faithfully recapitulate pathological features of human pancreatic diseases. Meanwhile, pancreatic organoids serve as a promising research platform for personalized drug screening and translational regenerative medicine .

The mammary epithelium forms a bilayered structure, which can be classified into two principal lineages: luminal cells and basal cells, according to their spatial distribution. The majority of basal cells are terminally differentiated contractile myoepithelial cells, while a small subset of CD49⁺EpCAM⁻ basal cells possess properties of tissue-specific adult progenitor cells. The luminal cell population consists of two subtypes: mature luminal cells capable of sensing hormonal signals and mediating milk secretion, as well as luminal progenitor cells with restricted differentiation potential. Accumulating studies have verified that the hierarchical differentiation mechanism of mammary epithelial cells is highly intricate. Alterations in physiological conditions such as pregnancy and aging, together with inherited mutations in breast cancer susceptibility genes, can markedly reshape the proportion and distribution of mammary epithelial subpopulations. In vitro culture techniques for mammary epithelial cells have provided crucial support for investigating the regular regulatory mechanisms and malignant transformation of mammary cells, facilitating fundamental research advances in mammary gland biology. Nevertheless, it remains challenging to establish an in vitro culture system that enables long-term stable cultivation and fully sustains all mammary epithelial lineages. Conventional culture approaches fail to efficiently preserve progenitor cells that serve as potential cells of origin for various breast cancer subtypes, which greatly hinders in-depth research on early oncogenic mechanisms of breast tumors. In contrast, mammary epithelial organoids derived from primary mammary tissues support sustained long-term passaging and completely retain all native mammary epithelial cell lineages. This model faithfully recapitulates the biomarker expression patterns of mammary tissues and stably reproduces the aberrant expansion phenotype of luminal progenitors triggered by BRCA1 heterozygous mutation, representing an excellent experimental system for exploring the mechanisms underlying mammary tumorigenesis and disease progression.

The kidney is a structurally sophisticated and highly hierarchically organized human organ, composed of approximately one million functional nephrons responsible for blood filtration. Each nephron comprises diverse specialized cell populations and consists of the renal corpuscle and highly convoluted tubular structures, which ultimately connect to the collecting duct system. While nephron numbers vary with age and health status, the overall nephron endowment is primarily established during embryonic renal development. Most kidney diseases lead to irreversible nephron damage and loss, underscoring the urgent demand for novel therapeutic strategies to complement conventional pharmacological interventions. Primary and immortalized renal cell lines have been widely utilized to characterize specific renal cellular properties; however, these in vitro models cannot reconstruct the complete histological architecture of native kidney tissue. Furthermore, cell immortalization inevitably disrupts endogenous cell cycle regulation, thereby interfering with the accurate interpretation of disease-associated molecular mechanisms. Although animal models offer physiologically relevant experimental systems, their applications are constrained by inherent interspecies differences and ethical limitations, making them incapable of faithfully recapitulating human renal pathophysiology. The lack of authentic human kidney models severely impedes in-depth exploration of renal physiological functions and pathological mechanisms. In recent years, organoid technology has evolved into a state-of-the-art biomedical research tool. Featuring polarized tissue structures and robust intercellular communication, organoids achieve superior simulation of the in vivo tissue microenvironment. The advancement of kidney organoid systems has pioneered new research avenues for investigating renal development, high-throughput drug screening, and precise disease modeling.

The human stomach features a structurally sophisticated 3D glandular epithelium that can be anatomically and functionally partitioned into two discrete compartments. The gastric corpus (fundus) is the main region responsible for secreting gastric acid and digestive enzymes, while the gastric antrum (pylorus) is mainly populated by mucus-producing cells and hormone-secreting endocrine cells. Research on gastric disorders currently depends heavily on conventional animal models and two-dimensional cell culture platforms, neither of which can faithfully reconstruct the complex physiological microenvironment and immune responses of the human stomach. As an advanced stem cell-derived culture system, gastric organoids recapitulate the intrinsic three-dimensional microenvironment of human gastric tissue and support optimal cell survival and proliferation. These features allow gastric organoids to closely replicate the physiological traits of native human gastric tissue, supporting more precise disease modeling and pathological research. Benefiting from their elaborate structure and authentic functional phenotypes, gastric organoids hold prominent promise for fundamental biological studies and translational medicine. By recapitulating the in vivo gastric microenvironment, such organoid models enable thorough dissection of the cellular and molecular mechanisms governing stomach development and disease progression.

Cardiovascular disease (CVD) ranks as the global leading cause of mortality and imposes substantial economic pressure on healthcare systems worldwide. Conventional biomedical studies predominantly adopt cell lines for disease modeling and drug screening, yet such in vitro models fail to recapitulate the full structural complexity of native in vivo tissues. To address these limitations, organoid culture systems have been established to restore pivotal biological features, including the physiological cellular microenvironment and intercellular crosstalk. The rapid advancement of organoid engineering and biomimetic models has innovated fundamental biological research, human pathogenic mechanism exploration, and drug response assessment, significantly accelerating the development of novel therapeutic strategies for diverse diseases. Cardiac organoids are structurally organized miniature cardiac constructs self-assembled by cardiac progenitor cells, cardiomyocytes, endothelial cells and fibroblasts within a three-dimensional microenvironment. They faithfully mimic the biological properties of endogenous human cardiac tissues and recapitulate the histogenetic processes, physiological functions and temporal developmental characteristics of the human heart. Owing to these superior biomimetic features, cardiac organoids have emerged as a powerful platform for cardiovascular disease modeling, high-throughput drug screening and toxicological evaluation, serving as an indispensable core tool for basic cardiac functional research and the development of personalized therapeutic regimens.

The prostate is an essential male gonadal organ, and its secretions account for approximately 30% of human seminal fluid. While the overall morphology of the prostate varies among species, the hierarchical cellular architecture of prostatic acini is highly conserved. Multiple in vitro culture studies using primary prostate epithelial cells have focused on characterizing prostate stem cells. These studies confirm that basal cells possess bipotent differentiation capacity, capable of generating both basal and luminal cell lineages, thereby exhibiting typical stem cell properties. Nevertheless, conventional in vitro culture models have notable limitations: they fail to recapitulate the native tissue structure of the prostate in vivo and struggle to sustain physiological expression levels of the androgen receptor. Mouse models have laid a vital experimental foundation for investigating prostate biological mechanisms, yet findings derived from these models cannot be directly translated to human prostate tissue. The primary contributing factor lies in prominent interspecies differences in the expression patterns of stem cell markers. Classic prostate stem cell markers including c-kit, CD177 and CD133 are exclusively expressed in human prostate basal cells, whereas in mice, they are detected in basal cells as well as subsets of luminal cells. At present, stable and mature human prostate research models remain scarce, which substantially impedes the clinical translation of basic research outcomes. Prostate organoids can faithfully recapitulate the physiological structure of the prostate and undergo efficient genetic and phenotypic modification via inhibitor treatment, retroviral transfection, CRISPR/Cas9 gene editing and other approaches. Featuring simple operation, cost effectiveness and high stability, they serve as a superior alternative experimental model.

As the largest functional organ of the human body, the skin performs multiple physiological functions including physical barrier defense, sensory signal transduction and the regulation of body temperature homeostasis. Structurally, it consists of three layers: the epidermis, dermis and subcutaneous tissue. The epidermis is composed of densely arranged keratinocytes, which form the stratum corneum to resist external stimuli and injuries. The dermis is a sophisticated connective tissue abundant in mechanoreceptors, sensory nerves, blood vessels, sweat glands, hair follicles, extracellular matrix and fibroblasts. Subcutaneous adipose tissue mainly undertakes energy storage and reserves diverse growth factors. Furthermore, the skin is equipped with a complete local immune defense system. Epidermal Langerhans cells and dermal dendritic cells constitute the innate immune barrier of the skin. Once local infection occurs, peripheral leukocytes can be recruited to participate in immune responses and injury defense. Skin diseases represent highly prevalent public health conditions worldwide. More than 5.4 million new skin cancer cases are reported each year, and approximately 500,000 patients receive clinical repair treatment for burns and various cutaneous wounds. At present, mouse models remain the primary in vivo tool for investigating skin development and pathological mechanisms of skin disorders. Nevertheless, prominent interspecies differences exist between human and mouse skin, especially regarding wound repair mechanisms, which severely restrict the clinical translation of animal experimental findings. Skin organoids exhibit tremendous application potential in exploring skin developmental mechanisms, drug screening and regenerative medicine, with their research value reflected in three main aspects. Firstly, they facilitate research on skin developmental mechanisms. As superior in vitro models, skin organoids help dissect how chemical signals modulate skin maturation and systematically elucidate the developmental rules of human skin, effectively overcoming limitations such as the scarcity of human clinical samples and species bias in animal models. Secondly, they support disease modelling and high-throughput drug screening. These models faithfully recapitulate pathological phenotypes including atopic dermatitis, hereditary skin diseases, skin cancers, as well as skin damage induced by ionizing radiation and chemical stimulation, providing a stable and reliable experimental platform for clarifying disease pathogenesis, developing innovative therapeutic regimens and conducting high-throughput drug screening. Thirdly, they advance research on regenerative medicine and clinical wound repair. Skin organoids can be adopted to analyze the pathophysiological progression of surgical trauma, accidental wounds and burn injuries, possessing great value in cutaneous wound regeneration and repair. Meanwhile, they show promising prospects for facial aesthetic reconstruction and the treatment of disorders characterized by skin appendage defects such as alopecia. Patient-derived skin organoids established via three-dimensional culture also offer novel research strategies for individualized mechanistic study and precise targeted therapy of hereditary skin disorders.

As the colonization site of endometrial progenitor cells, severe injury to the endometrial basal layer acts as the core cause of refractory uterine diseases. Severe endometrial damage triggered by surgical trauma such as dilation and curettage or viral infection completely disrupts the cyclic regeneration rhythm of the functional endometrial layer, thereby inducing various menstrual disorders including amenorrhea and hypomenorrhea. Meanwhile, persistent chronic inflammation mediates aberrant tissue repair processes, drives progressive endometrial fibrosis, and markedly inhibits epithelial regeneration and angiogenesis. Excessive abnormal deposition of fibrous connective tissue gradually replaces the normal extracellular matrix architecture, ultimately leading to irreversible severe impairment of uterine reproductive function. At present, mainstream clinical interventions include hysteroscopic adhesiolysis, intrauterine balloon or catheter placement, and postoperative adjuvant hormonal therapy. Nevertheless, these therapeutic approaches generally suffer from high recurrence rates and limited clinical efficacy and cannot achieve radical cure. Compared with conventional research models, endometrial organoids support long-term stable in vitro expansion, steadily retain epithelial biological characteristics, and accurately recapitulate the physiological responses of human endometrium to sex hormones. This model has become a central experimental tool for endometrial drug screening, tissue injury repair and regenerative medicine research.

Vascular complications such as cardiovascular diseases, atherosclerosis, diabetic retinopathy and diabetic nephropathy have become urgent global public health challenges. Traditional cell culture techniques are easy to implement and cost-effective, yet they have inherent limitations. Cell arrangement is artificially fixed, critical in vivo signal concentration gradients are absent, and only planar cell-cell contacts can be established, making it difficult to faithfully reconstruct authentic human physiological microenvironments. In recent years, vascular organoids have evolved into innovative in vitro disease models. Compared with conventional monolayer cell culture systems, vascular organoids reconstruct the sophisticated physiological architecture of blood vessels and enable precise elucidation of organ-specific functional traits and disease pathogenesis, serving as central experimental tools for investigating macroangiopathy and microangiopathy. Among them, vascular organoids generated from induced pluripotent stem cells (iPSCs) possess distinctive application advantages. This organoid system supports dynamic crosstalk between diverse cell populations and the extracellular matrix, forming hierarchically organized functional structures within biomimetic microenvironments. Composed mainly of endothelial cells and mural cells, vascular organoids re-establish bidirectional regulatory and inductive interactions between cells. They accurately mimic in vivo pathophysiological responses, as well as cellular turnover and functional compensation mechanisms intrinsic to native organs. The multicellular vascular units derived from these organoids can be assembled with organoids of the brain, kidney, pancreas, intestine, heart and other solid organs to generate vascularized artificial tissues with higher structural complexity and controllability. Meanwhile, iPSC-derived vascular organoids preserve the epigenetic signatures of patient donors, enabling the establishment of personalized drug screening platforms and offering novel support for mechanistic research and drug development targeting cardiovascular disorders associated with vascular injury. iPSC-derived vascular organoids exhibit diversified research value. On the one hand, this model recapitulates the full spectrum of vascular development under both physiological and pathological conditions, acting as an ideal experimental platform to probe mechanisms underlying cardiovascular aging. Although cellular reprogramming can partially reverse senescent phenotypes, iPSCs retain the telomere length and epigenetic characteristics of donors. By comparing vascular organoids derived from healthy individuals of different age groups and patients with cardiovascular diseases, combined with senescence-inducing approaches including long-term culture and external stress stimulation, researchers can systematically dissect the mechanisms triggering age-related vascular lesions. Cells obtained from elderly donors inherently possess shorter telomeres, which continuously erode during cell division. Such cells are more prone to senescence-associated aberrant epigenetic modifications and functional impairment, providing a natural research system to uncover the mechanisms of vascular aging. On the other hand, living organoid biobanks established using multiple patient samples deliver high-quality resources for basic mechanistic research, translational medicine and personalized precision healthcare. Patient-derived organoids faithfully recapitulate individual disease characteristics and predict drug responses, facilitating the development and optimization of individualized therapeutic regimens. For instance, stem cell organoids generated from cystic fibrosis patients display drug response profiles highly consistent with human clinical phenotypes, representing low-cost and high-efficiency tools for drug screening. Furthermore, quantitative readouts such as intestinal swelling in organoids can serve as novel biomarkers for auxiliary clinical diagnosis.

Hormones secreted by the thyroid gland play an indispensable role in organ development and the regulation of internal homeostasis. Over the past two decades, animal models and traditional cell lines have been widely adopted for investigating organ developmental mechanisms, drug screening, and toxicological assessment. Nevertheless, interspecies differences greatly hinder in-depth research into human-specific physiological processes, and conventional cell models lack the three-dimensional architecture of native human organs. Although ex vivo tissue slices preserve complete cellular composition, they are plagued by multiple limitations including difficult access to healthy specimens, incapability of long-term culture, and high susceptibility of cells to dedifferentiation. The emergence of organoid technology effectively overcomes these drawbacks. As three-dimensional multicellular biomimetic structures constructed in vitro, organoids faithfully recapitulate the morphological architecture and physiological functions of native organs, and are mainly divided into two categories: pluripotent stem cell-induced organoids and primary tissue-derived organoids. Studies have revealed that tissue-derived organoids can be successfully generated even if tissue-resident adult stem cells have not been clearly identified. This indicates that in vitro culture systems are capable of activating dormant progenitor cells, expanding rare stem-like cells, or reprogramming differentiated cells to acquire stem cell properties. Among them, pluripotent stem cell-derived organoids can fully recapitulate the whole process of embryonic development with abundant cell yields. In contrast, tissue-derived organoids feature relatively simple structures and limited cell output, making them more suitable for studies on tissue injury and repair mechanisms. Organoid technology has become a core tool for translational thyroid medicine research and exhibits great potential in exploring thyroid developmental mechanisms, establishing disease models and developing regenerative therapies. Combined with cutting-edge technologies such as single-cell multi-omics sequencing, CRISPR gene editing, co-culture systems and microfluidic organ-on-a-chip platforms, thyroid organoid models enable systematic analysis of thyroid physiological regulatory mechanisms and precise identification of novel therapeutic targets. In the future, only by unifying global experimental standards and strictly complying with clinical manufacturing specifications can such in vitro biomimetic models be safely and efficiently applied to clinical treatment and realize the clinical translation of basic research findings.

The inner ear mainly consists of the cochlea and vestibule, which are responsible for auditory perception and body balance regulation respectively. Inner ear hair cells and sensory neurons are highly vulnerable to external damage and can be impaired by multiple factors including genetic variations, long-term noise exposure, ototoxic drug stimulation and aging. Epidemiological data indicate that more than 1.5 billion people worldwide suffer from varying degrees of hearing impairment, among whom approximately 30% require clinical intervention. Meanwhile, 7.4% of the population will experience vestibular vertigo during their lifetime. At present, research progress on regenerative therapies for inner ear function is relatively slow. The key bottleneck lies in the lack of stable and efficient pathophysiological models to meet the requirements of preclinical validation before clinical translation. Conventional ex vivo inner ear tissue and cell models derived from animals have obvious limitations, such as morphological differences across species, low cell induction efficiency and inconsistent genomic characteristics. In addition, harvesting inner ear tissue is technically challenging; the procedure tends to cause irreversible damage to surrounding structures, and non-invasive imaging techniques cannot support refined and visualized observation. Against this research backdrop, organoid technology, with its unique strengths, has gradually emerged as a promising novel research tool in inner ear studies. Inner ear organoids are generated from stem cells or progenitor cells. They faithfully recapitulate the biological features of native inner ear tissues in multiple dimensions, including gene expression profiles, cellular composition, tissue architecture and physiological functions. This model can mimic the in vivo extracellular microenvironment and modulate the proliferation and differentiation of stem and progenitor cells via specific inducing factors to directionally generate specialized inner ear functional cells. Using the inner ear organoid system, researchers can observe the complete and dynamic developmental process of the inner ear in vitro and successfully construct functional human hair cells together with neural connections. To date, numerous studies have adopted stem/progenitor cell-derived inner ear organoids to deeply dissect the pathological mechanisms of inner ear neural injury and screen active compounds capable of counteracting drug ototoxicity and facilitating the repair and regeneration of hair cells. The establishment and application of inner ear organoid models provide innovative strategies and a reliable experimental platform for mechanistic investigation, diagnosis and clinical treatment of vestibular vertigo and sensorineural hearing loss.

Chronic nasal disorders and nasal mucosal infections are highly prevalent upper respiratory diseases worldwide, and their recurrent episodes continuously exacerbate the burden on social healthcare systems. As the primary defensive barrier of the upper respiratory tract, the nasal epithelium represents a highly specialized dynamic mucosal tissue. It integrates physical barrier protection, mucociliary clearance and sophisticated innate immune responses, and directly governs the initiation and progression of various nasal diseases. Dysfunction of the nasal epithelium is not merely a secondary pathological manifestation; instead, it acts as a critical initiating and driving factor for multiple nasal lesions such as chronic rhinosinusitis, allergic rhinitis and viral nasal infections. At present, basic research on the nasal mucosa mainly relies on animal models and immortalized cell lines. Nevertheless, these systems possess unavoidable inherent limitations, including interspecies biological disparities, aberrant cellular differentiation phenotypes, and an inability to fully reconstruct the three-dimensional tissue architecture of the human nasal mucosa. These drawbacks greatly hinder the mechanistic investigation of nasal diseases and translational research on precise therapeutic strategies. Nasal organoids can recapitulate the self-assembly characteristics, cellular heterogeneity and disease-specific pathological phenotypes of nasal epithelial tissues within a three-dimensional culture microenvironment. Currently, this model has been adopted for research covering mucosal infection mechanisms, inflammation-induced tissue remodeling and the functional regulation of epithelial ion channels. It provides a reliable in vitro research platform for elucidating the pathogenesis of nasal disorders including chronic rhinosinusitis and advancing individualized precision therapy.

Teeth perform masticatory and phonetic functions and also affect facial appearance as well as patients’ psychological status. Dental tissues are highly mineralized structures with distinct mineralization levels and hardness among different components. Enamel forms the outer bulk of the dental crown and represents the most highly mineralized tissue in the human body. During tooth development, dental epithelial stem cells undergo directed differentiation into ameloblasts, which mediate enamel formation. Following tooth eruption, ameloblasts undergo apoptosis, and mature enamel thereby permanently loses its capacity for self-repair and regeneration. At present, enamel defects caused by trauma or bacterial infection are mainly restored with synthetic dental materials. Nevertheless, conventional dental restorative materials have multiple drawbacks, such as microleakage, poor osseointegration and retention, limited service life, and incapability of complete reconstruction of dental structure and function. Organoid culture systems established from epithelial stem cells have been widely adopted for biological and pathological research on various human epithelial tissues. Human dental epithelial organoids can stably express stemness markers of epithelial cell rests of Malassez and sustain long-term in vitro expansion. Unlike most epithelial organoid systems, these odontogenic organoids can maintain stable growth without exogenous supplementation of epidermal growth factor. Furthermore, organoids retaining stem cell properties possess amelogenic differentiation potential and can recapitulate the biological characteristics and differentiation trajectories of dental epithelial stem cells and epithelial cell rests of Malassez in vitro. As a novel in vitro research platform, dental epithelial organoids facilitate in-depth analysis of the biological features, cellular plasticity and differentiation regulatory mechanisms of dental epithelial stem cells, offering innovative avenues for developing therapeutic strategies for dental tissue regeneration. Tooth germs are collected from embryonic day 14-16 mouse molars and incisors. Dental epithelium and dental mesenchyme are isolated and dissociated into single cells, followed by high-density recombination in collagen droplets for ex vivo organ culture. After 2-7 days of in vitro culture, the complexes are transplanted under the mouse kidney capsule to drive cell differentiation and tooth structure formation.