Exploring the different types of organoids: A gateway to advanced research
Organoids are self-organizing three-dimensional (3D) tissues derived from stem cells that replicate the complexity of human organs.
They offer a revolutionary approach to studying human biology and disease by closely replicating the structure and function of human organs in the lab. The cells that result in the development of organoids are primarily tissue-derived cells (TDCs), induced pluripotent stem cells (iPSCs), and cancer cells.
Organoids mimic human tissues in vivo, offering valuable insights into tissue organization, regeneration, and drug responses. They retain the genetic and histological characteristics of the original tumor, making them a powerful platform for personalized cancer therapy and drug screening.
In vitro 2D cell cultures have limitations as they are physiologically distinct to conditions in vivo. In this respect, animal models are no doubt valuable in understanding disease mechanisms, but these also come with challenges, such as the differences in biology and ethical issues. Thus, research in 2D cell cultures needs to be validated in a 3D environment with multiple cell types interacting with each other to more accurately recreate cellular dynamics.
3D cultures, such as organoids, provide insights into various diseases, such as those associated with genetic disorders, infections, or the various types of cancer, presenting a valuable alternative and complement to animal models in biomedical research.
Applications of organoids in research and medicine
Organoids have significant applications in research and medicine, offering enhanced disease modeling, drug discovery, and personalized medicine. They provide more accurate representations of human diseases, enabling drug screening, toxicity testing, and personalized treatment strategies while advancing our understanding of human development and infectious diseases, including COVID-19.
Disease modeling
Organoids have shown great promise in disease modeling by providing a more accurate representation of human disease mechanisms, including neurodevelopmental disorders, cancer, and infectious diseases.
As organoids closely resemble human organs, they offer unique advantages over traditional animal models. They enable drug screening, personalized medicine, and the study of disease progression in a human context.
Drug discovery and testing
Organoids are an advanced tool in drug discovery, offering improved drug response prediction, efficacy evaluation, toxicity testing, and pharmacokinetics analysis. They also enable personalized treatment strategies, regenerate tissues for transplantation, and bring basic research closer to clinical practice, though challenges remain in their application.
Personalized medicine
Organoids from patient stem cells offer a personalized approach to medicine by capturing individual phenotypic variability to predict disease outcomes and treatment responses. They can also be used for diagnostics, disease prognosis, and even organoid-based transplantation, with ongoing clinical trials exploring their potential in personalized therapies.
They offer a promising tool in precision medicine by:
- Enabling the testing of personalized drug responses
- Predicting treatment efficacy
- Stud
Developmental biology studies
Pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs), have facilitated the creation of organoid models. These models advance our understanding of human development and disease, overcoming previous ethical and technical barriers.
Organoids replicate the morphogenetic processes that drive tissue and organ formation in human development. They play a crucial role in studying cellular differentiation by providing a 3D environment where stem cells can differentiate into various specialized cell types.
With advancements in bioengineering and signaling factors, they increasingly mimic the structure and function of human organs, making them valuable tools for disease modeling and drug development.
Studies on infectious disease
Organoids provide a human-specific platform for studying infectious diseases. Moreover, organoids allow researchers to investigate pathogen-host interactions, disease mechanisms, and potential treatments for viral, bacterial, and parasitic infections.
These models have been applied to study diseases like Zika, COVID-19, and Helicobacter pylori infections, revealing pathogen-induced responses and providing preclinical models for drug development and mechanistic exploration of infection biology.
Research has demonstrated that SARS-CoV-2 infects and damages cortical neurons, impairing their synaptic connections. It also revealed that antiviral drugs can inhibit viral replication and restore affected neurons, highlighting a potential treatment for COVID-19-related neurological symptoms.
Types of organoids and their applications
The classification of organoids is often based on the organ systems they mimic, each offering unique insights and applications. From understanding intricate processes like brain connectivity to exploring liver detoxification pathways or intestinal nutrient absorption, organoids provide a dynamic and customizable platform for scientific exploration. Classifying organoids by the organ systems they replicate is crucial because it directly relates to their intended function and area of study. Organoids mimic the structural and functional properties of specific organs, making them valuable tools for understanding organ-specific development, physiology, and disease mechanisms.
This classification highlights the diverse applications of organoids, such as modeling organ-specific diseases, testing targeted therapies, and studying organ-level responses to drugs or environmental factors. By organizing organoids according to the organ systems they replicate, researchers can align studies with precise biological contexts, ensuring more targeted and meaningful insights. From understanding intricate processes like brain connectivity to exploring liver detoxification pathways or intestinal nutrient absorption, organoids provide a dynamic and customizable platform for scientific exploration.
The sections below highlight various types of organoids and their applications:
Brain organoids
Brain organoids are in vitro cell culture systems derived from human induced pluripotent stem cells (iPSCs), which are reprogrammed from adult somatic cells to an embryonic-like pluripotent state.
These organoids self-organize into complex structures that mimic key features of the developing human brain, including neural cell types, synapses, and myelination, closely resembling the early stages of brain development.
Applications
Recent advances in differentiating neural organoids, including cerebral, hippocampal, and retinal models, provide insights into neurodevelopment and disease pathogenesis, offering a complementary approach to traditional animal models for understanding the human nervous system.
Brain organoids provide an in vitro model for studying neurodevelopmental disorders like autism spectrum disorders, microcephaly, and Zika virus-induced brain malformations. They are also used to explore the effects of drugs on the brain and to investigate neurodegenerative diseases such as Alzheimer's and Parkinson's. Additionally, these models help researchers understand how the human brain develops and how abnormalities can lead to cognitive disorders3.
SARS-CoV-2 (the causative pathogen of COVID-19) was demonstrated to infect brain organoids and cause the loss of excitatory synapses in cortical neuron cells4. The viral replication was inhibited by Sofosbuvir, an FDA-approved anti-hepatitis C virus (HCV) treatment. This finding shows the use of organoids in understanding the long-term neurological/psychiatric sequelae of COVID-19 and for screening drugs.
Another study showed that human cerebral organoids could be used for screening drugs against the currently incurable and fatal disease Creutzfeldt–Jakob Disease (CJD) caused by CJD prions5. Treating the organoids with pentosan polysulfate (PPS) slowed down the prion propagation (prophylaxis) and lowered propagation after infection (treatment), showing the potential of 3D brain organoid cultures in drug screening.
Liver organoids (hepatic organoids)
Liver organoids or hepatic organoids, developed from stem cells or tissue samples, are assessed through passaging, cell proliferation, and expression of specific markers for cholangiocytes and hepatocytes to evaluate differentiation and functionality.
Applications
Liver organoids are being increasingly used for drug testing, particularly in assessing hepatotoxicity (liver toxicity) and evaluating new therapies for liver diseases like cirrhosis and hepatitis. They also serve as models for liver regeneration and transplantation studies. For example, it has been shown that liver organoids with Kupffer cells and other aggregates were a suitable model for non-alcoholic fatty liver disease (NAFLD)6. Additionally, liver organoids were used to study diseases such as α1-antitrypsin deficiency, Alagille syndrome, hepatitis C infection, liver cancer, and liver fibrosis, etc.
A microfluidic device-based multi-organ system using several types of organoids (liver, heart, and lung) could metabolize the drug capecitabine into 5-fluorouracil. When the organoids were expanded to include analogs for the liver, cardiac, lung, endothelium, brain, and testes, the tissues interacted with each other to metabolize the prodrug ifosfamide in the liver organoid to chloroacetaldehyde. Other examples have been covered in the other article on organoids7,8.
Intestinal organoids (human intestinal organoids)
Intestinal organoids are cell cultures that accurately replicate essential features of intestinal tissue, such as cellular diversity and the ability for stem cell renewal. Derived from either pluripotent stem cells or adult stem cells, these organoids have transformed the study of human intestinal biology.
Applications
Organoids are increasingly being used to study gastrointestinal diseases such as Crohn's disease, ulcerative colitis, and colorectal cancer. They are also used for research on gut microbiota interactions, nutrient absorption, and inflammatory bowel diseases (IBD). A combination of organ-on-a-chip technology and organoids was assembled into a duodenum intestine chip9. The chip showed that it recreated the relevant functions seen in the human body, such as the presence of drug transporters, intestinal barrier function, and cell polarization.
The expression of the drug-metabolizing enzyme CYP3A4 in duodenum intestine-chip (with combined organoids and organs-on-chips technology emulating intestinal tissue architecture and functions relevant for the study of drug transport, metabolism, and drug-drug interactions) was higher than that in the immortalized cell line of human colorectal adenocarcinoma, Caco-2 cells, showing its application in analyzing the pharmacokinetics of drugs. Intestinal organoids have been used to study host-pathogen interactions, such as SARS-CoV-2, Cryptosporidium parvumi, astroviruses, and Salmonella typhimurium10.
The construction of a biobank of intestinal organoids from cystic fibrosis patients has helped in assessing the use of gene editing to correct genetic defects11. Specifically, the use of SpCas9-adenine base editing (ABE) (post-spacer adjacent motif [PAM] recognition sequence: NGG) and xCas9-ABE (PAM recognition sequence: NGN) on selected organoids demonstrated functional repair, highlighting the potential of organoids in cutting-edge research.
Lung organoids (lung organoid culture)
Human lung organoids are derived from pluripotent stem cells. They replicate key structures and cell types of developing human airway organoids, including bronchi and alveoli. These organoids are also valuable for regenerative medicine, tissue engineering, and drug testing.
Applications
Lung organoids are essential for studying respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease (COPD), and lung cancer. These models also provide a platform for drug testing, including therapies targeting viral infections such as COVID-19, and for studying lung development and regeneration. In one study, patient-derived tumor organoids (PDOs) were produced from a patient with non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) mutations12.
Drug screening on these PDOs revealed that gefitinib, a drug that blocks EGFR tyrosine kinases and prevents EGF-induced proliferation in cell culture, could alone inhibit cancer cells at a higher rate than the combination of carboplatin, pemetrexed, and gefitinib13. Hence, this organoid-based screening helped design a treatment regimen for the patient with gefitinib monotherapy that showed promising results. This research shows the use of organoids in clinical prediction and personalized medicine.
Lung cancer organoids that mimicked the primary tumors obtained from lung cancer patients were used to screen for drugs based on the genotype14. For example, the drug response was influenced by the genomic alteration; a BRCA2-mutant organoid responded to olaparib, an EGFR-mutant organoid responded to erlotinib, and an EGFR-mutant/MET-amplified organoid responded to crizotinib, highlighting the use of lung organoids for drug screening in personalized medicine.
Skin organoids
Skin organoids, derived from pluripotent stem cells, form structured skin-like tissues with progenitor cells and hair follicles resembling fetal skin.
Applications
Skin organoids offer promising models for studying skin biology, disease, and regeneration, although current models still lack some critical skin structures. They are used to investigate skin disorders like eczema, psoriasis, and melanoma. They also play a role in wound healing studies and can be utilized for testing dermatological products or assessing the skin's response to UV damage and environmental stressors.
Skin organoids obtained from human induced pluripotent stem cells (hiPSCs) were used to identify that the SARS-CoV-2 infects hair follicles with the epithelial marker KRT17, which affects hair development, highlighting one of the mechanisms of hair loss caused by COVID-1915. New insights were obtained when epidermal organoids were infected with the dermatophyte Trichophyton rubrum16. The application of epithelial and mesenchymal (EM) organoids on scleroderma skin (in mice) lowered the extent of skin fibrosis in the organoid treatment group compared to the scleroderma group17.
Kidney organoids
Kidney organoids derived from human stem cells are invaluable tools for studying kidney development and disease, effectively modeling glomerular and tubular conditions.
Applications
Kidney organoids are crucial for modeling kidney diseases such as polycystic kidney disease, glomerulonephritis, and nephrotoxicity. These models also help study kidney development, function, and response to drug treatments, particularly those aimed at treating renal failure or damage.
Kidney organoids have been used to model kidney injury, polycystic kidney disease, and SARS-CoV-2 infection18,19. The establishment of a kidney organoid-on-a-chip of polycystic kidney disease showed that cyst formation was due to glucose transport into the lumen of the outer epithelial cells of the model, showing the potential of organoids in improving our understanding of disease pathogenesis. Screening of kidney organoids facilitated the identification of the quinazoline derivate QNZ as an inhibitor of cyst growth in autosomal dominant polycystic kidney disease20.
However, challenges remain, as current organoids are still immature, and further advancements in protocols are required to achieve fully mature, transplantable kidney structures with functional components like nephrons and vascular flow.
Breast organoids
Breast organoids are generated from mammary stem cells or iPSCs, mimicking the structure of human breast tissue, including the ductal and alveolar components.
Applications
Breast organoids are being used to understand tumor progression, metastasis, and the effects of chemotherapy or targeted therapies. They also aid in the study of hormonal regulation and lactation. For example, breast organoids were used to screen drugs based on specific breast cancer mutations, such as the suitability of olaparib and niraparib for BReast CAncer gene 1 (BRCA1) mutations, tamoxifen with interleukin-1beta (IL-1β) and platelet-derived growth factor (PDGF)-BB receptor blockers for malignant ER+breast cancer organoids, and gefitinib, afatinib, everolimus, and AZD8055 for ER2 overexpressing cells21.
Cardiac organoids
Cardiac organoids are in vitro models derived from pluripotent stem cells and induced to develop into tissue that resemble the myocardium (heart muscle) and other heart structures.
Applications
Cardiac organoids provide a platform for studying heart diseases, including congenital heart defects, arrhythmias, and myocardial infarction (heart attack). They are also used to test the effects of drugs on cardiac function and to explore heart regeneration and repair mechanisms. Cardiac organoids were used to assess the cardiotoxicity of drugs, such as doxorubicin, demonstrating their potential for cardiotoxicity screening. Many environmental toxins (glyphosate, lead, mercury, thallium) and drug molecules (verapamil, vernakalant, astemizole, to name a few) have been screened using cardiac organoids22,23.
Prostate organoids
Prostate organoids are cultured from prostate epithelial cells that closely mimic the architecture and cellular complexity of the prostate gland, providing a more accurate representation of both prostate cancer and normal tissue than traditional 2D models.
Applications
Prostate organoids enable the study of tumor behavior, metastasis, and drug responses. They also aid in understanding the biology of benign prostatic hyperplasia and prostate development. PDOs were used to predict the response to drugs/therapy, such as ALK inhibitors and ET domain inhibitors. Clinical trials, such as NCT04723316, NCT03952793, etc, are also using prostate organoids in their studies24.
For instance, the NCT04723316 trial in the United Kingdom intends to build a framework for providing molecular profiling of ctDNA and/or tumor tissue to patients with advanced malignancies. The NCT03952793 study intends to establish an organoid culture approach using metastases from patients with advanced prostate cancer to test different anticancer compounds.
Retinal organoids
Retinal organoids are created from retinal progenitor cells and mimic the architecture of the human retina, including photoreceptors, retinal ganglion cells, and other retinal layers.
Applications
Retinal organoids are crucial for studying retinal diseases such as age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy. They are also used in research on gene therapies and retinal regeneration, offering the potential for vision restoration therapies. Drug candidates have been tested for several retinal drugs using retinal organoids, such as fenofibrate, which was found to prevent photoreceptor death25. Further, retinal organoids have served as potent models to show the toxicity of drugs, including sildenafil, digoxin, and tinidazole, showing their use in drug toxicity screening26.
Thyroid organoids
Thyroid organoids are developed from thyroid stem cells or iPSCs and replicate the architecture of the thyroid gland, including follicular cells and thyrocytes that produce thyroid hormones.
Applications
Thyroid organoids are used to study thyroid diseases, such as hypothyroidism, hyperthyroidism, and thyroid cancer. They also help researchers understand thyroid development and function, as well as the effects of different thyroid hormone therapies. For example, patient-derived papillary thyroid cancer organoids showed drug responses specific to patients in the drug sensitivity analysis27.
The BRAFV600E inhibitors vemurafenib and dabrafenib were toxic to samples with BRAF gene mutations, while the wild-type was resistant. Additionally, cell division in these organoids was increased by estradiol in the presence of estrogen receptor α (ERα), highlighting the potential use of ERα-specific antagonists for treatment27.
Organoid culturing techniques
Organoids are derived from various cell sources, including iPSCs, adult or fetal tissue, and cancer cells, offering versatile platforms to study tissue-specific processes. The initial stage in organoid synthesis is separating certain cell types or stem cells from their original tissue.
Tissue dissociation processes, such as enzymatic digestion through trypsin and collagenase, or mechanical dissociation, are applied to break down the ECM to identify stem cells, crypts, or organ-specific progenitors for cultivation. For example, stem cells in intestinal tissue can be isolated from crypt structures, and then cultured to form intestine organoids. Specific cell types from human tissues can be isolated for organoid cultures through techniques like fluorescence-activated cell sorting and magnetic-activated cell sorting.
Antibodies targeting CD133, a marker of pancreatic progenitor cells, have been used to isolate pancreatic stem/progenitor cells from human pancreatic tissues. These isolated cells can be cultured into organoids that model pancreatic development and disease.
Antibodies against epithelial cell adhesion molecule (EpCAM), a marker of hepatic progenitor cells, are commonly used to isolate liver progenitors28. These cells can develop into liver organoids for studying liver regeneration and disease modeling.
For neural organoid cultures, antibodies targeting Nestin or SOX2, markers of neural stem/progenitor cells, are used to isolate neural progenitors from human brain tissue. These progenitors contribute to organoids that replicate neural development and diseases.
Lung epithelial progenitor cells are isolated using antibodies against markers like EpCAM and integrin α6 (CD49f). These progenitors can generate lung organoids for respiratory disease research29.
Antibodies targeting CD24, a marker of intestinal stem cells, have been utilized to sort cells for the generation of intestinal organoids. This is particularly useful in studying gastrointestinal diseases30.
The use of epidermal growth factor (EGF) and Noggin (BMP/TGF-β inhibitor) has also been reported. Specific fibroblast growth factors (FGF; for example, FGF7 and FGF10 for lungs) and nicotinamide are used based on the tissue type. Characterization of the organoids can entail screening for relevant markers using antibodies and sequencing approaches.
Cells are then seeded into matrices or synthetic hydrogels such as the alginate hydrogel kit for 3D cell culture (ab241011), which provide structural support, while soluble factors like growth factors or small-molecule drugs guide differentiation, mimicking in vivo conditions for tissue-specific development.
Overview of methods for culturing organoids
Various methods have been developed for culturing organoids, including engineering approaches like microfluidic systems and fluidic shear conditions. These methods further enhance vascularization and specific cell culture protocols for different organ types.
Other innovations include:
- Hydrogel-based arrays for retinal organoids: Retinal organoid arrays (ROAs) were developed from mouse embryonic stem cells using biomimetic hydrogel arrayed round-bottom milliwells31. This compartmentalization of organoids at predefined locations can facilitate studying the dynamics and development of each organoid for high-throughput assays. The aggregation of organoids in the hydrogel avoids changing tissue culture plates, lowering the manual steps involved, allowing for “one-step handling” and for the future development of process automation.
- Co-culturing with microbes: This is an interesting advancement, given the role that microbes play in our body. The term “gut microbiome” refers to the expansive number and the integral functions of gut bacteria in human health and disease. Co-culturing organoids and microbes has emerged as a promising approach to analyzing these cell-microbe interactions, whether for gut microbes or pathogens. For example, the effects of the Zika virus were studied in brain organoid systems32, and the pathogenesis of SARS-CoV-2 was studied in several organoids19, such as alveolar organoids, lung airway organoids, lung organoids, and kidney organoids, etc. The use of intestinal organoid co-cultures with immune cells and microbes is a powerful tool for understanding the dynamics of the gut microbiome.
- On-chip culturing for long-term growth and real-time imaging: The concept of organoids-on-a-chip is being studied, as this allows for the physicochemical environment to be more tightly controlled, and the shape and size of organoids can be more uniform33. Thus, the exchange of nutrients and gas is better optimized, and the risk of contamination is reduced, overcoming some of the challenges of organoid culture. Including vasculature to increase the size and life of organoids is also being studied by co-culturing with endothelial cells and progenitor cells, as well as the use of genetic circuits and stimuli. The biomedical applications of these chips can be further enhanced with real-time imaging to assess the effects of stimuli on the organoids. For example, real-time imaging of tumor organoids on a microfluidic chip allowed the simultaneous screening of multiple drugs under multiple conditions. This system has the potential to be used for analyzing drug combinations to mimic patient responses and guide personalized medicine34,35.
- High-throughput screening platforms for drug discovery: The profiling of the adverse effects of drugs (the most commonly limiting step in the drug discovery pipeline) primarily relies on cell lines and animal models, each with the limitations outlined above. Organoid culture can overcome the limitations of 2D cell culture approaches by mimicking the 3D system of the organ7. They are more time- and cost-effective compared to animal models (which also have ethical challenges. For example, human liver organoids were cultured in 3D bioprinting and miniature organoid culture on pillar plates and were used to test the toxicity of several drugs. A promising drug screening system for nephrotoxicity was designed using a 3D in vitro human renal organoid model from donor kidneys36,37.
All these methods are aimed at improving reproducibility, efficiency, and physiological relevance.
Challenges in organoid culture systems
Organoid technologies have made significant progress but still face challenges, such as:
Heterogeneity in cell populations: Achieving the precise differentiation of human pluripotent stem cells (hPSCs) into a single, desired cell type is a complex challenge, often leading to heterogeneous cell populations that complicate their use in clinical applications.
Low experimental repeatability: Organoid culture systems often face low repeatability across different research groups, affecting consistency and reliability in results.
High cost of growth factors: The high cost of growth factors and nutrients required for organoid culture restrict the widespread use and accessibility of this technology.
Limited cellular development: PSC-derived organoids often fail to mature to an adult tissue-like stage, limiting their use in research and clinical applications.
Inconsistent extracellular matrix (ECM): The use of inconsistent ECM sources can introduce variability in organoid behavior and hinder their ability to accurately mimic the environment in vivo.
Inability to fully mimic in vivo environment: Current organoid systems cannot fully replicate the complex in vivo microenvironment, limiting their physiological relevance and maturity.
FAQs
What are the advantages of using organoids?
The most significant advantage of organoids is that they are a 3D culture of cells that more closely mimic the organ from which they were isolated. While cell lines are key in the initial stages of research, they face the challenges of altered genetic patterns, and limited physiological simulation (as they are 2D cultures). 3D cultures can better mimic the cell-cell connections/interactions and physicochemical microenvironments of organs. Animal models, whilst indispensable, are primarily challenged by ethical issues and interpreting the differences of species and subsequent extrapolation of results in humans7.
An added advantage of organoids is that they offer higher throughput, where arrays of organoids can be cultured for research or screening38. Additionally, research is now focusing on combining multiple organoid systems “on a chip,” and the use of microfluidics is enhancing these advantages. Organoids are being evaluated for their potential in regenerative medicine to circumvent transplantation processes. Beyond regenerative medicine and cancer, organoids serve as robust platforms for studying infectious diseases, genetic disorders, and developmental biology.
How are brain organoids used to study neuropsychiatric disorders?
Brain organoids are used to study neuropsychiatric disorders by modeling human brain development and replicating key neural features, allowing researchers to examine disease mechanisms. They help in testing drug responses and exploring genetic and environmental influences on conditions like autism, schizophrenia, and Alzheimer's.
What advancements have been made in creating liver organoids?
Advancements in creating liver organoids include the development of more complex models that mimic the structural and functional properties of the human liver, such as bile ducts and hepatocytes. These improvements enable better study of liver diseases, drug toxicity, and liver regeneration, as well as providing platforms for personalized medicine and organ transplantation research.
How do intestinal organoids help in drug absorption studies?
Intestinal organoids help in drug absorption studies by providing a more accurate in vitro model of the human intestinal lining, allowing researchers to observe how drugs interact with intestinal cells. These models mimic the absorption, metabolism, and transport processes of the intestines, facilitating the testing of drug efficacy and safety before clinical trials.
What is the role of organoids in studying interactions in tumor microenvironments?
Organoids are used to study interactions in the tumor microenvironment by recreating the complex cellular structures and interactions that occur in tumors. They allow researchers to investigate the mechanism by which cancer cells interact with surrounding stromal cells, immune cells, and ECM components, providing data about tumor progression, drug resistance, and therapeutic responses.
What are the challenges in culturing lung organoids?
Challenges in culturing lung organoids include maintaining the complex cellular diversity and architecture of the lung, as well as providing the appropriate microenvironment, such as oxygen levels and mechanical forces, that mimic the in vivo conditions. Additionally, achieving reproducibility and scalability while maintaining the functional properties of the organoids, including the cilia movement and gas exchange, remains a significant hurdle.
What are the ethical concerns of using human-derived organoids?
Ethical concerns about using human-derived organoids include issues related to consent, as donors must give informed permission for their cells to be used in research. Additionally, there are concerns about the potential for organoids to develop advanced capabilities, such as consciousness or sentience, raising questions about their moral status and the appropriate boundaries of their use in scientific experiments.
References
- Xu, H., Jiao, D., Liu, A., et al. Tumor organoids: applications in cancer modeling and potentials in precision medicine. Journal of hematology & oncology 15, 58 (2022)
- Yokota, E., Iwai, M., Yukawa, T., et al. Clinical application of a lung cancer organoid (tumoroid) culture system. Nature partner journal precision oncology 5, 29 (2021)
- Eichmüller, O.L., Knoblich, J.A. Human cerebral organoids — a new tool for clinical neurology research. Nature reviews neurology 18, 661-680 (2022)
- Mesci, P., de Souza, J.S., Martin-Sancho, L., et al. SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir. PLoS biology 20, e3001845 (2022)
- Groveman, B.R., Ferreira, N.C., Foliaki, S.T., et al. Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt-Jakob disease. Scientific reports 11, 5165 (2021)
- Harrison, S.P., Baumgarten, S.F., Verma, R., et al. Liver organoids: recent developments, limitations and potential. Frontiers in medicine 8, 574047 (2021)
- Qigu, Y., Sheng, C., Qiaoling, P., et al. Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine. MedComm 5, e735 (2024)
- Rajan, S.A.P., Aleman, J., Wan, M., et al. Probing prodrug metabolism and reciprocal toxicity with an integrated and humanized multi-tissue organ-on-a-chip platform. Acta biomaterialia 106, 124-135 (2020)
- Kasendra, M., Luc, R., Yin, J., et al. Duodenum intestine-chip for preclinical drug assessment in a human relevant model. Elife 9, e50135 (2020)
- Adeniyi-Ipadeola, G., Nwanosike, H., Ramani, S. Human intestinal organoids as models to study enteric bacteria and viruses. Current opinion in microbiology 75, 102362 (2023)
- Geurts, M.H., de Poel, E., Amatngalim, G.D., et al. CRISPR-based adenine editors correct nonsense mutations in a cystic fibrosis organoid biobank. Cell stem cell 26, 503-510.e7 (2020)
- Pan, Y., Cui, H., Song, Y. Organoid drug screening report for a non-small cell lung cancer patient with EGFR gene mutation negativity: a case report and review of the literature. Frontiers in oncology 13, 1109274 (2023)
- Narasimhan, V., Wright, J.A., Churchill, M., et al. Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases to direct personalized therapy. Clinical cancer research 26, 3662-3670 (2020)
- Kim, M., Mun, H., Sung, C.O., et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nature communications 10, 3991 (2019)
- Ma, J., Liu, J., Gao, D., et al. Establishment of human pluripotent stem cell-derived skin organoids enabled pathophysiological model of SARS-CoV-2 infection. Advanced science (Weinheim) 9, e2104192 (2022)
- Wang, X., Wang, S., Guo, B., et al. Human primary epidermal organoids enable modeling of dermatophyte infections. Cell death & disease 12, 35 (2021)
- Ma, J., Li, W., Cao, R., et al. Application of an iPSC-derived organoid model for localized scleroderma therapy. Advanced science (Weinheim) 9, e2106075 (2022)
- Tran, T., Song, C.J., Nguyen, T., et al. A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery. Cell stem cell 29, 1083-1101.e7 (2022)
- Vanslambrouck JM, Neil JA, Rudraraju R, et al. Kidney organoids reveal redundancy in viral entry pathways during ACE2-dependent SARS-CoV-2 infection. Journal of virology 98, e0180223 (2024)
- Tracy, T., Cheng, J.S., Trang, N., et al. A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery. Cell stem cell 29, 1083 - 1101.e7 (2022)
- Yen-Dun, T.T., Jui-Hu, H., Ling-Ming, T., et al. Breast cancer organoids derived from patients: a platform for tailored drug screening. Biochemical pharmacology 217 (2023)
- Xi, C., Na, L., Shengbo, H., et al. Assessment of doxorubicin toxicity using human cardiac organoids: a novel model for evaluating drug cardiotoxicity. Chemico-biological interactions 386 (2023)
- Forsythe, S.D., Devarasetty, M., Shupe, T., et al. Environmental toxin screening using human-derived 3D bioengineered liver and cardiac organoids. Frontiers in public health 6, 103 (2018)
- Waseem, M., Wang, B.D. Organoids: an emerging precision medicine model for prostate cancer research. International journal of molecular sciences 25, 1093 (2024)
- Eade, K., Giles, S., Harkins-Perry, S., et al. Toxicity screens in human retinal organoids for pharmaceutical discovery. Journal of visualized experiments 169, 10.3791/62269 (2021)
- Dorgau, B., Georgiou, M., Chaudhary, A., et al. Human retinal organoids provide a suitable tool for toxicological investigations: a comprehensive validation using drugs and compounds affecting the retina. Stem cells translational medicine 11, 159-177 (2022)
- Dong, C., Yawen, T., Zhichao, L., et al. Organoid cultures derived from patients with papillary thyroid cancer. The journal of clinical endocrinology & metabolism 106, 1410-1426 (2021)
- Laurent, D., Neil, D.T., Eva, S., et al. EpCAM and the biology of hepatic stem/progenitor cells. American journal of physiology - gastrointestinal and liver physiology 308, G233-G250 (2015)
- McQualter, J.L., Yuen, K., Williams, B., et al. Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung. Proceedings of the national academy of sciences of the United States of America 107, 1414-1419 (2010)
- Gracz, A.D., Ramalingam, S., Magness, S.T. Sox9 expression marks a subset of CD24-expressing small intestine epithelial stem cells that form organoids in vitro. American journal of physiology - gastrointestinal and liver physiology 298, G590-G600 (2010)
- Decembrini, S., Hoehnel, S., Brandenberg, N., et al. Hydrogel-based milliwell arrays for standardized and scalable retinal organoid cultures. Scientific reports 10, 10275 (2020)
- Marrazzo, P., Cricca, M., Nastasi, C. Are the organoid models an invaluable contribution to ZIKA virus research? Pathogens 10, 1233 (2021)
- Chengyu, H., Sheng, Y., Tianyi, Z., et al. Organoids and organoids-on-a-chip as the new testing strategies for environmental toxicology-applications & advantages. Environment international 184 (2024)
- Wang, H., Ning, X., Zhao, F., et al. Human organoids-on-chips for biomedical research and applications. Theranostics 14, 788-818 (2024)
- Schuster, B., Junkin, M., Kashaf, S.S., et al. Automated microfluidic platform for dynamic and combinatorial drug screening of tumor organoids. Nature communications 11, 5271 (2020)
- Shrestha, S., Lekkala, V.K.R., Acharya, P., et al. Reproducible generation of human liver organoids (HLOs) on a pillar plate platform via microarray 3D bioprinting. Preprint. bioRxiv 2024.03.11.584478 (2024)
- Ding, B., Sun, G., Liu, S., et al. Three-dimensional renal organoids from whole kidney cells: generation, optimization, and potential application in nephrotoxicology in vitro. Cell Transplantation 29, 963689719897066 (2020)
- Sugimoto, S., Sato, T. Organoid vs in vivo mouse model: which is better research tool to understand the biologic mechanisms of intestinal epithelium? Cellular and molecular gastroenterology and hepatology 13, 195-197 (2022)