Organoid Biobanks: Significance, Challenges, and Technologies
Significant and yet plenty of overarching issues
Organoid technology has been revolutionizing the field of biomedical research, and biobanks play a crucial role in advancing this tool. Organoids are three-dimensional, miniature, multicellular organ-like structures derived in vitro predominantly from stem cells or patient tissue.
Biobanks serve to collect, store, and distribute organoids and have thus emerged as important resources for researchers worldwide.
These biobanks serve as repositories of diverse organoid models. They enable scientists to study tissue or organ development, disease mechanisms, perform accurate drug testing, and develop personalized clinical approaches.
Organoid biobanks have ushered in new possibilities for medical research by providing access to a vast array of organoid models (1,2). These biobanks are comprised of various human tissues and organs, including the liver, lung, brain, intestine, and kidney. Biobanks also facilitate collaborative research, enabling scientists from different institutions to share resources and knowledge. One of the most significant advantages of organoid biobanks is their potential for disease modeling and drug screening while eradicating the need for animal models (3).
Organoids can be derived from patient-specific stem cells as well as patient tumors, allowing researchers to recreate individualized disease models in a laboratory setting. This approach holds tremendous promise for studying rare genetic disorders, cancer, infectious diseases, and neurodegenerative conditions. These biobanks provide a centralized resource for these disease models, accelerating drug discovery and research efforts.
Tumor organoids, in particular, have addressed previously unsurmountable challenges faced while working with cell lines such as tumor heterogeneity. In addition, these organoids replicate the complex and unique tumor microenvironment for each tumor subtype more efficiently than animal models (2,4). The ability of patient-derived organoids to closely recapitulate tumor characteristics has unlocked a new avenue to create tumor organoid biobanks. These biobanks consist of tumors from an array of patients with varied tissue sources. Sequencing of tumor organoid biobanks can also aid bioinformatics-driven identification of shared predominant mutations within indications.
Establishment and application of tumor organoid biobank
(Picture courtesy: Xie, Xuexue et al. “Tumor organoid biobank-new platform for medical research.” Scientific reports, 2023)
The overall workflow involved in creating a tumor organoid biobank involves:
(i) tumor tissue collection from surgical resections or biopsies
(ii) tissue processing
(iii) organoid culture using carefully optimized niche factors and extracellular matrix
(iv) organoid testing (studying growth and morphology, genetic and molecular characterization using DNA sequencing, RNA sequencing, immunohistochemistry, and fluorescence in situ hybridization) to identify mutations, gene expression patterns, etc.
(v) organoid cryopreservation at ultra-low temperatures
(vi) data management (patient data, clinical annotations, genetic profiles, experimental results, etc.) and integration (bioinformatics-enabled correlation of organoid data with clinical outcomes and genomic data for comprehensive analysis) (2).
However, construction of a tumor organoid biobank entails several logistic and ethical challenges. Logistic concerns are apparent at the levels of standardization, tumor procurement, safety regulation, organoid preservation, transport, and retrieval. The establishment and operation of organoid biobanks also raise important ethical and regulatory considerations. Ensuring informed consent, privacy protection, and ethical use of organoid samples are paramount (5). Regulatory bodies and scientific communities are actively working on developing guidelines to address these concerns and promote responsible biobank practices. Striking the right balance between scientific progress and ethical responsibility will be imperative to harnessing the complete potential of organoid biobanks.
The field of organoid biobanks continues to evolve rapidly. Researchers are working on refining organoid culture techniques, improving scalability, and enhancing the representation of different cell types within organoids. Efforts are also underway to develop standardized protocols and quality control measures for organoid production and characterization. Additionally, organoid biobanks are exploring collaborations with industry partners to facilitate drug discovery and translational research.
References:
1. Kretzschmar, Kai. “Cancer research using organoid technology.” Journal of molecular medicine (Berlin, Germany) vol. 99,4 (2021): 501-515. doi:10.1007/s00109-020-01990-z
2. Xie, Xuexue et al. “Tumor organoid biobank-new platform for medical research.” Scientific reports vol. 13,1 1819. 1 Feb. 2023, doi:10.1038/s41598-023-29065-2
3. Clevers, Hans. “Modeling Development and Disease with Organoids.” Cell vol. 165,7 (2016): 1586-1597. doi:10.1016/j.cell.2016.05.082
4. Xia, Tao et al. “Organoid models of the tumor microenvironment and their applications.” Journal of cellular and molecular medicine, vol. 25,13 5829–5841. 25 May. 2021, doi:10.1111/jcmm.16578
5. Boers, Sarah N et al. “Organoid biobanking: identifying the ethics: Organoids revive old and raise new ethical challenges for basic research and therapeutic use.” EMBO reports vol. 17,7 (2016): 938-41. doi:10.15252/embr.201642613