Researchers have developed a new class of biomaterials based on non-toxic, designed amyloid fibrils that can make thixotropic hydrogels for in vitro tumor modeling. The study, conducted by Singh, Patel, Navalkar, Kadu, Datta, Chatterjee, Mukherjee, Shaw, Gahlot, Shaw, Jadhav, and Maji, shows that the hydrogels can provide cues for cell adhesion, proliferation, and migration, while mimicking the physio-chemical milieu for the formation of tumors from various cancer cell lines and cells from xenograft tumors.
Outcomes:
- New biomaterials based on non-toxic, designed amyloid fibrils can make thixotropic hydrogels for in vitro tumor modeling
- The hydrogels can provide cues for cell adhesion, proliferation, and migration
- The hydrogels mimic the physio-chemical milieu for the formation of tumors from various cancer cell lines and cells from xenograft tumors
- The amyloid hydrogel can be a good candidate for 3D spheroid formation for patient-derived tumors, which will be studied in future
The study presents a new option for tumor modeling that could help in the development of anti-cancer drugs. Current preclinical models for drug assessment have limitations, including low throughput, time requirements, and high shear force. The amyloid hydrogels support a single 3D spheroid in a well with necrotic core formation at day 3 of culture, and showed increased drug resistance compared to 2D cell culture.
While the preliminary data suggests that all the amyloid hydrogels can support spheroid formation of various cancer cell lines, further studies such as microarray analysis and drug testing using xenograft or patient-derived tumor models are needed to select a particular hydrogel for developing tumor spheroids from specific cancer cells. Nonetheless, this new development is an exciting advancement in the field of tumor modeling and could contribute to more reliable preclinical models for the assessment of anti-cancer drugs.
Amyloid fibril-based thixotropic hydrogels for modeling of tumor spheroids in vitro
Singh; Patel; Navalkar; Kadu; Datta; Chatterjee; Mukherjee; Shaw; Gahlot; Shaw; Jadhav; Maji 2023
Full-text link: https://doi.org/10.1016/j.biomaterials.2023.122032
What this paper is about
- In this study, we present a class of biomaterials based on non-toxic, designed amyloid fibrils, which make thixotropic hydrogels for in vitro tumor modeling.
- The spheroids formed in these hydrogels showed increased drug resistance as compared to 2D cell culture.
- Mean pore sizes of the amyloid hydrogels ranged from 9 to 17 m. The plot of the storage modulus vs the frequency of the hydrogels is displayed using rheology measurements at 37 C. Rheological characterization revealed that at a lower frequency, the storage modulus G is higher than that of the loss modulus by approximately one order of magnitude indicating the formation of hydrogels.
What you can learn
- Thus, the failure rate of anticancer drugs during clinical trials is higher than that of any other therapeutics. This is mainly due to the absence of reliable preclinical models for the assessment of the drugs.
- To overcome all these limitations, biomaterial-based 3D cell culture systems or in vitro organoid models have gained interest for clinical outcomes and hence are becoming more prominent in drug discovery.
- Moreover, other factors include the time requirement, low throughput, and high shear force.
- The data showed that all these hydrogels support a single 3D spheroid in a well with necrotic core formation at day 3 of culture.
- Interestingly when testing FA1 gel with a cell suspension of xenograft-derived mouse tumor, we found that FA1 support tumor spheroid which possesses necrotic core, higher resistance of drugs compared to 2D cell culture, gene expression similar to the original tumor as well as Matrigel, used as a positive control. This clearly indicates that our amyloid hydrogel can be a good candidate for 3D spheroid formation for patientderived tumors which will be studied in future.
- Although our preliminary data suggests that all the amyloid hydrogels can support spheroid formation of various cancer cell lines further detailed studies such as microarray analysis and drug testing using xenograft or patientderived tumor models need to be done to select a particular hydrogel for developing tumor spheroids from specific cancer cells.
Core Q&A related to this research
What is the focus of the study described in the paper?
The focus of the study is the development of a class of biomaterials based on non-toxic, designed amyloid fibrils that can make thixotropic hydrogels for in vitro tumor modeling. The hydrogels provide cues for cell adhesion, proliferation, and migration, and can mimic the physio-chemical milieu for the formation of tumors from various cancer cell lines as well as cells from xenograft tumors.
What is the importance of the amyloid fibril-based thixotropic hydrogels in the development of anti-cancer drugs?
The amyloid fibril-based thixotropic hydrogels provide a biomimetic ECM platform for the screening of anticancer therapeutics. They can be used as a reliable preclinical model for the assessment of drugs, which can help to overcome the high failure rate of anticancer drugs during clinical trials.
What is the advantage of using 3D cell culture systems or in vitro organoid models for drug discovery?
Biomaterial-based 3D cell culture systems or in vitro organoid models have gained interest for clinical outcomes and are becoming more prominent in drug discovery. They can overcome the limitations of 2D cell culture, including the absence of reliable preclinical models, time requirements, low throughput, and high shear force.
What is the significance of the formation of tumor spheroids in the amyloid hydrogels?
The formation of tumor spheroids in the amyloid hydrogels is significant because it demonstrates that the hydrogels can support 3D spheroid formation of various cancer cell lines, which can mimic the physio-chemical milieu for the formation of tumors. The spheroids formed in these hydrogels also showed increased drug resistance compared to 2D cell culture, which can help to screen anticancer therapeutics.
What further studies need to be done to select a particular hydrogel for developing tumor spheroids from specific cancer cells?
Further detailed studies such as microarray analysis and drug testing using xenograft or patient-derived tumor models need to be done to select a particular hydrogel for developing tumor spheroids from specific cancer cells.
Basics Q&A related to this research
Q: What is a tumor spheroid?
A: A tumor spheroid is a 3D cell culture that mimics the microenvironment of a tumor and is used as a preclinical model for the assessment of anti-cancer drugs.
Q: Why is tumor spheroid formation important in the development of anti-cancer drugs?
A: Tumor spheroid formation is important in the development of anti-cancer drugs because it provides a reliable preclinical model for the assessment of the drugs, which can reduce the failure rate of the drugs during clinical trials.
Q: What are biomaterials based on amyloid fibrils?
A: Biomaterials based on amyloid fibrils are non-toxic, designed fibrils that make thixotropic hydrogels for in vitro tumor modeling.
Q: What are thixotropic hydrogels?
A: Thixotropic hydrogels are gels that are solid at rest but become fluid when subjected to shear stress or agitation.
Q: What is in vitro modeling?
A: In vitro modeling is the process of creating a laboratory environment that mimics a specific biological process or system.
Q: What is cell adhesion?
A: Cell adhesion is the process by which cells attach to a surface or other cells.
Q: What is cell proliferation?
A: Cell proliferation is the process by which cells divide and increase in number.
Q: What is cell migration?
A: Cell migration is the process by which cells move from one location to another.
Q: What is the physio-chemical milieu?
A: The physio-chemical milieu refers to the microenvironment surrounding a cell, including factors such as pH, temperature, and chemical composition.
Q: What are xenograft tumors?
A: Xenograft tumors are tumors that are formed by the transplantation of human or animal tumor cells into another species.
Q: What is a biomimetic ECM platform?
A: A biomimetic ECM (extracellular matrix) platform is a laboratory environment that mimics the natural extracellular matrix surrounding cells in vivo.
Q: What is drug resistance?
A: Drug resistance is the ability of cancer cells to survive and continue to grow despite exposure to anti-cancer drugs.
Q: What are 3D cell culture systems?
A: 3D cell culture systems are laboratory environments that allow cells to grow and interact in three dimensions, mimicking the in vivo environment more closely than traditional 2D cell culture systems.
Q: What are in vitro organoid models?
A: In vitro organoid models are laboratory environments that mimic the structure and function of specific organs in the body.
Q: What is a necrotic core?
A: A necrotic core is a region within a tumor spheroid where cells have died due to a lack of oxygen and nutrients.
Q: What is gene expression?
A: Gene expression is the process by which information in a gene is used to create a functional protein.
Q: What are patient-derived tumors?
A: Patient-derived tumors are tumors that are grown in the laboratory from cells taken directly from a patient’s tumor.
Q: What is microarray analysis?
A: Microarray analysis is a laboratory technique that allows researchers to study the expression of many genes at once.
Q: What is drug testing?
A: Drug testing is the process of evaluating the effectiveness and safety of potential new drugs.
