1. Development of bone disease models
The creation of organoids allows for easy and accurate modeling of the desired disease.
Compared with animal models, organoid disease models can eliminate species differences, more realistically mimic the microenvironment of human pathology, and are more conducive to elucidating disease mechanisms through modeling.
1) Osteoporosis model
Osteoporosis is a disease that affects the entire skeletal system, leading to a decrease in bone density and quality and deterioration of the bone microstructure.
This process weakens bones, making them more susceptible to fracture.
Osteoporosis can have multiple causes and leads to increased bone brittleness, which can have a significant impact on a person's overall health and quality of life.
Animal models of osteoporosis are generally generated by surgical removal of gonads, drug application (e.g., glucocorticoids), and gene editing, which are costly, long, and have many uncontrollable factors.
In contrast, modeling can be readily achieved in bone organ models by adding cytokines that regulate osteogenesis and promote the osteogenic process or inhibit it so that bone resorption occurs faster than osteogenesis.
2) Bone Cancer Model
Bone cancer is a primary or secondary tumor that occurs in the bone or its supporting tissues.
Current bone tumor models are primarily created by collecting and transplanting clinical tumor tissue into cultures or animals.
Because of the low incidence of primary tumors in bone and the fact that the skeleton is one of the most frequently metastasized organs, much of the current research has focused on metastatic tumors in bone.
A study designed a 3D model by CT scanning the microstructure of the femoral epiphyseal trabecular bone and constructing a 3D scaffold using isoprenaline.
Culturing MSCs in the scaffold promotes differentiation into osteoblasts, generating a microenvironment similar to that of bone trabeculae, and dispersing breast cancer cells into the model to construct a 3D model of breast cancer bone metastasis.
Organoid culture using tumor cells enables tumor cells to grow in a 3D space that mimics the human microenvironment, which is more conducive to subsequent research and screening for therapeutic approaches.
3) Bone defect modeling
A bone defect is a condition in which the structural integrity of the bone is disrupted due to surgical trauma or other reasons.
Current bone defect models include cranial defects, long bone or segmental defects, partial cortical defects, and cancellous bone defect models.
Bone defect models are mostly obtained from animals by artificially destroying bones. The availability of bone-like organs would perfectly mimic the microenvironment in the human body, reducing animal loss and cutting costs.
4) Osteoarthritis model
Osteoarthritis is considered the most prevalent chronic degenerative joint disease and is an age-related sterile inflammatory disease.
Since osteoarthritis has multiple etiologies, there are a number of modeling approaches available, such as post-traumatic osteoarthritis caused by manual trauma, or corresponding models can be created by intra-articular injection of drugs, gene knockouts, etc.
It can modulate the immune response of organoids to model osteoarthritis.
An organoid model of the bone-cartilage junction was designed to mimic the physiological conditions at the joint by mechanical stimulation and different cell culture bases. This is simpler and more economical than building animal models.
5) Hereditary Bone Disease Models
Hereditary bone diseases are skeletal lesions caused by developmental disorders due to genetic factors.
Prior to the introduction of stem cells into organoid systems to mimic alterations in genetic material, gene editing methods can be used to knock out or edit relevant genes in order to construct genetic disease models in vitro.
In vitro models of genetic diseases in other organs have been established by constructing organoids.
A study was completed by knocking out the GLA gene in iPSCs by gene editing and culturing them into kidney-like organs exhibiting Fabry nephropathy for subsequent studies.
Combining gene editing technology with bone-like organs allows for the construction of models of osteogenetic diseases, such as congenital chondrodysplasia, congenital osteogenesis imperfecta, and Robinow syndrome, and the in vitro study of their pathogenesis and therapeutic approaches.
2. Bone repair and regeneration
Clinical treatment of large bone defects is currently limited and presents many challenges to patients, such as scarcity of bone tissue sources and severe rejection.
However, regenerative medicine makes it possible to repair tissue and organ damage in a more feasible and effective way.
Organoids, which are micro-organs grown in vitro, have emerged as a promising strategy for bone tissue regeneration because they offer a convenient and rejection-free autograft option.
By obtaining their own stem cells and inducing differentiation into bone in vitro, patients can obtain homologous bone that can be transplanted into the body for growth and development.
Despite numerous attempts to construct bone-like organs for bone regeneration, most current strategies are limited in their ability to mimic the complexity of bone structure and developmental processes.
They usually mimic only one phase or structure of the skeleton, which is a single spatio-temporal analog.
This fails to fully replicate the complexity of bone formation and fails to achieve the necessary level of complexity required for clinical applications.
Therefore, new approaches are urgently needed to develop more advanced bone-like organs that can closely resemble the complex structure and function of natural bone tissue.
With further research and development, organoids have the potential to be a viable alternative to bone grafts and bone filler materials, providing patients with safer and more effective treatment options for large bone defects.
3. Drug discovery and toxicity assessment
Current drug discovery for human diseases faces several limitations, such as the diversity of individual patients, unpredictable adverse outcomes, and time-consuming drug testing processes.
Due to the complexity of constructing bone-like organs, it is not yet possible to use organoids for drug discovery and screening, but organoids have been successfully used in other fields.
A study involving the cultivation of mouse distal intestinal organoids in 96-well plates, in which more than 2,000 pharmacologically active compounds were screened for inhibition of potassium ion transport, resulted in the identification of one of the most promising compounds.
Similarly, an organoid model of primary liver cancer was constructed, demonstrating that in vitro liver tumor organoids can express the same gene profiles as in vivo and have the characteristics of primary liver cancer.
This allows for high-throughput screening of oncology drugs on the model, which could potentially lead to the discovery of new treatments for liver cancer.
4. Personalized medicine
Precision medicine is an innovative approach that uses genetic information to diagnose and treat diseases in a personalized way.
One of the techniques used is to generate organoids from the patient's primitive cells, which have the same genetic makeup as the patient.
Organoids can be used to screen potential treatments and select drugs in vitro, thereby reducing the risk of side effects during treatment.
This approach is particularly useful for tumors, which are known for their genetic heterogeneity.
Precision medicine can also be applied to primary and secondary tumors related to the skeleton, as well as chronic conditions such as osteoarthritis and osteoporosis.
By creating individual patient organoids, precision medicine can provide treatments tailored to each patient's unique genetic makeup, leading to more effective outcomes.
The creation of organoids from a patient's primitive cells is a cutting-edge technology that has shown promising results in precision medicine.
Organoids can mimic the behavior of human organs, making them ideal tools for drug detection and personalized therapy.
Because tumors vary from person to person, organoids derived from a patient's tumor can be used to screen potential treatments and select the best drug for that particular patient, thereby increasing the likelihood of a successful outcome.
5. Research on developmental biology
Developmental biology is a field of study that delves into the complex processes that occur during the growth and development of organisms from the cellular to the molecular level.
By using organoids (artificially grown organ-like structures) derived from undifferentiated stem cells, scientists can study the production and development of tissues and organs in microenvironments that mimic the conditions of living organisms.
For example, bone-like organs can reproduce the osteogenic processes (formation of bone tissue) that occur in living organisms, including intrachondral and intramembranous osteogenesis.
By examining the differential expression of genes and proteins during osteogenesis, researchers can gain insight into the molecular mechanisms involved in bone development and growth.
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