Tumor organoid biobank-new platform for medical research

www.nature.com/scientificreports OPEN Tumor organoid biobank‑new platform for medical research Xuexue Xie 1, Xinyu Li 2 & Wei Song 3* Organoids are a new type of 3D model for tumor research, which makes up for the shortcomings of cell lines and xenograft models, and promotes the development of personalized precision medicine. Long-term culture, expansion and storage of organoids provide the necessary conditions for the establishment of biobanks. Biobanks standardize the collection and preservation of normal or pathological specimens, as well as related clinical information. The tumor organoid biobank has a good quality control system, which is conducive to the clinical transformation and large-scale application of tumor organoids, such as disease modeling, new drug development and highthroughput drug screening. This article summarized the common tumor types of patient-derived organoid (PDO) biobanks and the necessary information for biobank construction, such as the number of organoids, morphology, success rate of culture and resuscitation, pathological types. In our results, we found that patient-derived tumor organoid (PDTO) biobanks were being established more and more, with the Netherlands, the United States, and China establishing the most. Biobanks of colorectal, pancreas, breast, glioma, and bladder cancers were established more, which reflected the relative maturity of culture techniques for these tumors. In addition, we provided insights on the precautions and future development direction of PDTO biobank building. Tumor is a heterogeneous disease1–5, which seriously threatens human life and health. In recent years, substantial progress has been made in immunological and targeted therapy for malignant tumors. The main obstacle to the development of new drugs is the clinical translation of scientific results, and the key to overcoming this obstacle is the selection of high-quality preclinical research m odels6,7. Existing research models, such as immortalized cell lines, patient-derived tumor xenografting (PDX), and animal models, have their own advantages and disadvantages (Table 1). Immortalized cell lines can be gene edited and allow high-throughput drug screening, with the advantages of easy access and strong experimental reproducibility. But most tumor cell lines have lost the heterogeneity of primary tumors after long-term selective culture in a single environment in vitro. Another preclinical model is PDX, which can mimic tumor heterogeneity and microenvironment, but is very costly, timeconsuming, and has a low success rate. Although animal model established by injecting tumor cell lines or tumor cell spheres into immunodeficient mice can create a relative in vivo environment, it may still affect the accuracy of the experiment due to species differences or lack of immune microenvironment. Therefore, researchers are committed to developing a preclinical model that can truly reflect the characteristics of patients, and organoids have been widely recognized by the medical community as a new type of 3D model. Tumor organoids are formed by mechanically and enzymatically extracting tumor cells from fresh tumor tissue and cultured them in specific matrices, which can reflect the heterogeneity of parental tumor tissue8–10. PDO are high-quality model for preclinical research. Many of the major discoveries in basic and translational medicine benefited from exploratory research on large biobanks11–15. At present, many academic and commercial groups have established their own PDTO biobanks, but how to standardize quality control of biobank still needs a unified standard. The establishment of standards will help the promotion of organoid models. This article summarized the current development status of PDTO biobanks and provided insights on the precautions and future development direction. Overview of PDTO biobanks As a novel 3D culture model, organoids16–18 are in vitro miniature organs composed of epithelial cells. Sato et al.19 first proposed that LGR5 + mouse intestinal stem cells can proliferate indefinitely through organoids. There is increasing evidence that PDTOs retain the histological and genomic characteristics20–25 of parental tumor for use 1 First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China. 2Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China. 3Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324, Jingwuweiqi Road, Jinan 250021, People’s Republic of China. *email: Scientific Reports | (2023) 13:1819 | https://doi.org/10.1038/s41598-023-29065-2 1 Vol.:(0123456789) www.nature.com/scientificreports/ Models Immortalized cell line Tumor spheres PDX PDTO Cultivating way 2D 3D 3D 3D Maintenance and passage Easy Moderate difficulty Difficult Moderate easy Growth speed Rapid Rapid Slow A little slow Heterogeneity of tumor Lack Lack Preserve Preserve Tumor microenvironment Lack Lack Partly retention Partly retention Established success rate Low Low Slightly lower Moderate Cost Low Slightly higher High Slightly higher Gene editing Editable Editable Not editable Editable High-throughput drug screening Allow Allow unallowed Allow Large scale application Allow Not recommended unallowed Allow Normal controls None None None Have Genetic tumor model None None Have Have Table 1.  Comparison of preclinical patient-derived tumor research models. in personalized m edicine26 and new drug development27–30, with great potential compared to other models31. In basic research, exon and transcriptome sequencing analysis can be used to find key mutations and transcriptome changes, which is helpful to further explore the mechanism of tumor genesis, development and treatment resistance or sensitization32–34. The PDTO biobanks centrally manage and utilize organoid information. Since Sato et al. developed the first organoid model19 from mouse small intestine in 2009, substantial progress has been made in the field35–37. At present, many commercial and academic groups have established their own PDTO biobanks. Here, we summarized the current PDTO biobanks and related information (Additional file 1). Comprehensive PDTO biobanks. Organoids, as "patients in the laboratory", can better reflect tumor heterogeneity and drug response. The organoid biobank, established by the Hubrecht Institute, Utrecht University Medical Center and the Royal Netherlands Academy of Arts and Sciences is one of the most comprehensive organoid biobanks. It collected more than 1,000 organoids from a variety of organs and diseases, including breast, colon, head and neck tumors, intestinal, liver, lung, ovarian, and pancre (...truncated)