1. Biological studies
The applications of organoids in biological research mainly include the application of organoids to study cell development, differentiation and tissue formation, as well as biological system function and gene function.
1) Study of biological processes such as organ development
By utilizing phenomics research facilities and techniques for high-resolution imaging and exhaustive phenotyping of organoids, it is possible to accurately and dynamically track the development of organoids at different points in time.
This includes a detailed reconstruction of the evolution of organoid volume and morphology, tissue structure and cellular arrangement, as well as dynamic changes in organoid self-assembly and network interactions connectivity.
These analytical methods enable in-depth excavation of the key factors affecting the development and differentiation fate of organoid organs and reveal the subtle molecular mechanisms involved in the developmental process, thus providing comprehensive and in-depth insights into the understanding of the development and differentiation of real organs in the human body.
Based on phenomics of organoids, a series of methods can also be developed to identify and classify different cell types in organoids, to explore the cell types that play key regulatory roles in organoid development, as well as the developmental time trajectories of organoid tissues, and to reveal the developmental characteristics and functions of organoids.
2) Study of the functioning of biological systems
The study of biological system function aims to analyze the synergistic patterns among cell populations in tissues, reveal the regulatory mechanisms of the system under diverse conditions, and understand key life processes such as signaling, metabolic pathways and regulatory pathways.
However, due to the complexity of biological systems, there are many challenges in resolving their internal interactions and regulatory mechanisms.
Organ-like models are able to reconstruct tissue systems in vitro that are similar to those in vivo, enabling persistent dynamic observations that can provide insight into optimization strategies for living systems.
By modeling different environmental conditions and physiological states, it is possible to more accurately understand how living systems coordinate and adapt in the face of diversity challenges.
3) Study of gene function
Genes, as carriers of genetic information, play multiple important roles in organisms, including protein coding, cell cycle and regulation of metabolic pathways.
During the self-assembly and development of organoids, which have a genetic background of human origin, the activation state of different genes varies in response to specific inducing factors, thus contributing to the formation of different organoids similar to those found in the human body.
In a wide range of human diseases, genetic mutations or dysfunctions play a key role in the onset and progression of the disease.
For example, the heritability of schizophrenia is as high as 70% to 90%, so it is important to study the genetic mechanisms of the disease to discover therapeutic targets.
The emergence of three-dimensional humanoid organs provides an effective model for revealing the role of genes in disease.
By comparing the phenotypic differences between normal and mutant genes at the organoid level, the effects of mutations on organoids can be analyzed in depth.
2. Medical research
The applications of organoids in medical research mainly include: disease modeling, drug screening, toxicology testing, precise diagnosis and treatment of diseases.
1) Disease Modeling
The application of organoid models enables accurate disease modeling, providing strong support for in-depth analysis of disease mechanisms and development of new drugs.
On the one hand, genetic diseases can be modeled by introducing specific gene mutations to reveal the role of mutated genes in the disease process; on the other hand, models can also be built using cells derived from the disease patients themselves.
In the first method, a suitable cell or tissue model can be selected according to the type of the target disease, and a disease-related mutation or abnormal expression of a specific gene can be introduced by techniques such as gene editing or viral vectors.
This allows phenomics analysis to be carried out at multiple levels to assess disease-induced changes in cellular morphology, alterations in metabolic pathways, and changes in signaling pathway activity, thereby providing insight into disease mechanisms.
In the second approach, stem cells retaining the patient's genetic background are obtained through somatic cell reprogramming, combined with induced pluripotent stem cell differentiation techniques to generate multiple organ types in vitro for patients with specific diseases, and combined with techniques such as microfluidic chips to rebuild the disease microenvironment.
This type of organ model retains the patient's own genetic characteristics and therefore more accurately reflects the disease state.
2) Revealing disease-causing mechanisms
Changes in the morphology, biomarkers and gene expression of class organs can be revealed by analyzing the abnormal phenotypes of relevant class organs and tissues in disease states.
This helps to identify key molecules and pathways that are closely related to diseases and reveal abnormalities in the biological pathways and signaling that lead to diseases, thus providing insight into the mechanisms of disease occurrence and development.
In addition, these identified abnormal phenotypic changes can be used as diagnostic markers for diseases. By detecting the presence of relevant molecular markers in organoids and combining them with test results from clinical patients, early diagnosis of diseases and monitoring of their conditions can be achieved.
Meanwhile, finding the upstream drivers of these abnormal changes, such as key genes and signaling pathways that are abnormally activated, will not only help to further understand the disease mechanisms, but may also be potential drug targets for disease treatment.
3) Drug screening
Conventional drug screening mainly relies on two-dimensional cell cultures and model animal models, but there are still some limitations in the assessment of drug efficacy.
Taking patient-derived tumor-like organs as an example, this novel research tool not only preserves the native biology of the tumor, but also allows for stable transmission, which offers unique advantages in the development and screening of tumor drugs.
In the use of organoids for drug screening, by observing the phenotypic changes of organoids after drug treatment and combining them with phenomics techniques, a comprehensive assessment of drug efficacy can be made and the prediction of drug side effects can be realized.
Further analysis of the causes of changes in organoid phenotypes can help reveal the molecules, pathways and proteins that drugs may affect, thus pinpointing the targets of drug action and providing insight into how drugs affect biological processes and reveal their mechanisms of action.
4) Drug toxicology testing
The problem of organ toxicity has been a major cause of drug development failures and post-marketing withdrawals.
Although cell lines and animal models are commonly used for toxicology screening, they are often difficult to accurately predict adverse reactions in humans.
To address this problem, the emergence of 3D organoid technology may open new avenues and provide a more accurate method for toxicity prediction.
A three-dimensional cell culture system that mimics human tissues and organs, such as skin, liver, and myocardium, allows for toxicological testing of drugs under conditions that more closely resemble the in vivo environment.
These organoid models preserve the diversity of cellular and tissue structures in vivo.
By observing the phenotypic changes in organoids after drug treatment, the toxic effects of drugs in vivo can be predicted more accurately.
5) Precise diagnosis and treatment of diseases
Precision drug therapy means treating the disease while reducing damage to other organs.
Taking tumor treatment as an example, drug treatment has gradually shifted from chemotherapy to immunotherapy, and patients' survival and quality of life have been improved, but accurate pathological diagnosis and individualized medication still face challenges in clinical practice.
Current treatment options each have their limitations, whether it is chemotherapy or immunosuppressants, and most of them still have low efficiency rates, and patients are often at risk of trial and error.
The application of tumor-like organ chips provides a solution to this problem.
Tumor organoid microarray drug susceptibility testing involves culturing organoids on organoid microarrays that are highly consistent with the patient's tumor, and which are capable of reproducing the characteristics of the tumor in the patient's body.
Therefore, these organs can be used as “tumor scapegoats” to screen the best drug regimen and achieve precise treatment of the disease.
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