Patient Derived Organoids (PDO)
Patient derived organoids are three dimensional, miniaturized, and simplified versions of human organs (or tumors) grown in vitro.
Organoids in Medical Research
Organoids are three-dimensional, miniaturized, and simplified versions of human organs grown in vitro from stem cells. As a result, they play an important role in medical research due to their ability to closely mimic the structure and function of real human tissues. Consequently, they are becoming increasingly important in this field.
1. Human Relevance and Precision
Because organoids are derived from human cells, they are more representative of human biology compared to traditional models like animal testing or two-dimensional cell cultures. This human relevance allows for more accurate disease modeling and drug responses. For instance, organoids can be used to study human brain, liver, lung, or intestinal diseases with a level of detail that animal models cannot provide.
2. Personalized Medicine
One of the most promising uses of organoids is in personalized medicine. In particular, organoids can be created from an individual’s stem cells, allowing researchers to test how different drugs affect that person’s disease. This way, treatments can be tailored to the patient’s unique genetic and molecular profile. This is especially useful for conditions like cancer, where treatments vary based on genetic mutations.
3. Disease Modeling
Organoids offer a way to replicate key features of diseases. This enables researchers to study how a disease develops and progresses in a controlled environment. As a result, it is especially useful for complex diseases such as cancer, neurodegenerative diseases like Alzheimer’s, and genetic disorders. For example, brain organoids have been used to study the Zika virus infection, which was linked to microcephaly in newborns. By using this model, researchers better understand how the virus affects brain development.
4. Drug Discovery and Toxicology
Since organoids mimic human tissues, they provide a more reliable platform for drug testing and toxicology studies. Therefore, pharmaceutical companies can test the efficacy and safety of new drugs on organoids before advancing to clinical trials. This approach reduces the time and cost associated with drug development. Moreover, it minimizes the need for animal models.
5. Reduced Ethical Concerns
Organoids serve as an ethical alternative to animal testing, addressing many concerns in medical research. Furthermore, they allow scientists to perform experiments that would be difficult or ethically questionable in humans. This includes studying the early stages of human development or testing toxic substances.
6. Studying Development and Regeneration
Organoids allow researchers to study human organ development and tissue regeneration. In this way, they provide insights into developmental biology, regenerative medicine, and congenital disorders. As such, they are particularly valuable for understanding early human development and applications in tissue engineering.
7. Cancer Research
In cancer research, tumor organoids derived from patient biopsies mimic the tumor environment. These tumor organoids allow for real-time analysis of how cancer cells grow, evolve, and respond to treatments. Therefore, they provide a useful tool for precision oncology. By testing various therapies on these patient-specific tumor models, researchers can identify the most effective treatment options.
8. Understanding Rare Diseases
Organoids offer a way to study rare diseases at a cellular level. For example, researchers can use CRISPR and other gene-editing techniques to introduce specific mutations into organoids. Through this, they can model rare conditions and explore potential treatments for those diseases.
9. Conclusion
Organoids are a powerful tool for bridging the gap between traditional models and real human biology. As a result, they have the potential to revolutionize personalized medicine, improve drug development, reduce animal testing, and advance our understanding of human diseases.
Webinar
In this webinar, Dr. Nikolina Radulovich discussed patient-derived organoids (PDOs) and their essential role in cancer research. Here is a summary of her talk:
What Are Organoids?
Organoids are three-dimensional cell cultures grown from patient tumor samples, crucial for studying disease mechanisms and drug testing. They are created by breaking down patient tissues and placing the cells in a supportive matrix. With the right signals, the cells organize into structures that resemble the original tissue. These models are widely used for studying diseases, drug screening, and exploring how tumors interact with the microbiome.
Ensuring Long-Term Culture Growth
One of the key challenges is ensuring long-term culture growth. The team focuses on generating organoids that can grow beyond 10 passages, making them useful for extended research. However, not all tissues are equally easy to culture—some, like pancreatic cancer, are more successful, while others, such as ovarian or breast, present greater difficulties.
Quality Control and Reliability
The biobank performs rigorous quality control to ensure that organoid models are accurate and reliable, closely matching the genetic and structural complexity of the original tumor. This includes extensive testing like histology and genomic profiling to maintain high-quality models.
Applications in Drug Screening
PDOs are also highly effective in drug screening. The webinar highlighted their use in the COMPASS study, where PDOs helped predict patient responses to treatments, showing promise for personalized medicine.
Collaboration Opportunities
For researchers or companies interested in working with PDOs, the biobank offers collaboration opportunities. This includes access to organoid models, support with protocols, and assistance with drug screening projects.
Conclusion
In summary, PDOs offer a powerful tool for cancer research, providing reliable and renewable models that can help predict drug responses and advance our understanding of disease mechanisms.
About Cancer Organoids
Cancer organoids are three-dimensional models of tumors grown from patient-derived cancer cells. In particular, they closely mimic the architecture and function of the original tumor, making them valuable in cancer research and treatment development.
1. Personalized Cancer Therapy
Cancer organoids can be derived from a patient’s tumor cells, creating a personalized model of their cancer. As a result, researchers and clinicians can test different treatments directly on the patient’s cancer. By observing the organoid’s responses, clinicians can tailor treatment plans, potentially improving outcomes and minimizing side effects.
2. Mimicking Tumor Heterogeneity
Cancer is highly heterogeneous, with different regions of the same tumor having different mutations and behaviors. Therefore, cancer organoids replicate this heterogeneity, offering a more accurate model of tumor complexity compared to traditional 2D cultures. As a result, researchers can study how different parts of the tumor respond to treatment and why some areas resist therapy.
3. Improved Drug Screening
Cancer organoids are valuable for high-throughput drug screening. Thus, pharmaceutical companies and research labs can test thousands of compounds on these organoids to identify potential cancer drugs. Because organoids are derived from human cells, they often provide more accurate predictions of drug efficacy and toxicity.
4. Understanding Tumor Microenvironment
The tumor microenvironment—the surrounding cells, blood vessels, and immune cells—plays a critical role in cancer progression. Cancer organoids can be co-cultured with other cell types to better mimic the tumor’s environment. Through this approach, researchers study how tumors interact with their surroundings, contributing to advances in treatment strategies like immunotherapy.
5. Modeling Metastasis
Organoids can be used to study cancer metastasis, which is the spread of cancer from the primary tumor to other parts of the body. Through these models, researchers gain insights into how cancer spreads and identify ways to prevent metastasis.
6. Resistance Mechanisms
Drug resistance is a major challenge in cancer treatment. Cancer organoids enable researchers to investigate how cancer cells develop resistance to therapies. By modeling tumor evolution under treatment pressure, organoids help identify new therapeutic strategies.
7. Rare and Difficult-to-Treat Cancers
For rare cancers or those that are hard to study using traditional models, organoids provide a powerful tool. Tumor organoids derived from these cancers can be used to explore potential treatment options and understand their biology in ways that are not possible using animal models or 2D cultures. This is especially valuable for cancers that lack established treatment protocols or clinical trials due to small patient populations.
8. Gene Editing and Cancer Research
Organoids can be genetically modified using techniques like CRISPR to introduce or remove specific mutations found in cancers. This allows researchers to explore the role of particular genes in cancer development, progression, and drug response. These experiments provide insights into cancer genetics and potential therapeutic targets for novel treatments.
9. Reducing Animal Testing
While animal models have traditionally been used in cancer research, they often do not fully replicate human cancer biology. Cancer organoids, derived from human tissues, offer a more ethical and accurate alternative to animal testing. By reducing the reliance on animals, organoids can speed up the development of effective cancer treatments while addressing ethical concerns in research.
10. Research on Tumor Evolution
Cancer organoids can be grown over long periods, allowing researchers to study how tumors evolve over time, including genetic changes, treatment resistance, and interactions with surrounding tissues. This long-term modeling provides unique insights into the dynamics of tumor growth and how cancers adapt to different conditions, which is critical for improving long-term treatment strategies.
11. Conclusion
Cancer organoids represent a cutting-edge advancement in cancer research. They offer highly realistic models of tumors that are patient-specific and biologically complex. Consequently, they are crucial for improving personalized treatment, enhancing drug discovery, and reducing reliance on animal testing. Organoids are expected to play a key role in developing more effective cancer therapies.
