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Liu YY, Wu DK, Chen JB, Tang YM, Jiang F. Advances in the study of gastric organoids as disease models. World J Gastrointest Oncol 2024; 16:1725-1736. [PMID: 38764838 PMCID: PMC11099456 DOI: 10.4251/wjgo.v16.i5.1725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/23/2024] [Accepted: 03/25/2024] [Indexed: 05/09/2024] Open
Abstract
Gastric organoids are models created in the laboratory using stem cells and sophisticated three-dimensional cell culture techniques. These models have shown great promise in providing valuable insights into gastric physiology and advanced disease research. This review comprehensively summarizes and analyzes the research advances in culture methods and techniques for adult stem cells and induced pluripotent stem cell-derived organoids, and patient-derived organoids. The potential value of gastric organoids in studying the pathogenesis of stomach-related diseases and facilitating drug screening is initially discussed. The construction of gastric organoids involves several key steps, including cell extraction and culture, three-dimensional structure formation, and functional expression. Simulating the structure and function of the human stomach by disease modeling with gastric organoids provides a platform to study the mechanism of gastric cancer induction by Helicobacter pylori. In addition, in drug screening and development, gastric organoids can be used as a key tool to evaluate drug efficacy and toxicity in preclinical trials. They can also be used for precision medicine according to the specific conditions of patients with gastric cancer, to assess drug resistance, and to predict the possibility of adverse reactions. However, despite the impressive progress in the field of gastric organoids, there are still many unknowns that need to be addressed, especially in the field of regenerative medicine. Meanwhile, the reproducibility and consistency of organoid cultures are major challenges that must be overcome. These challenges have had a significant impact on the development of gastric organoids. Nonetheless, as technology continues to advance, we can foresee more comprehensive research in the construction of gastric organoids. Such research will provide better solutions for the treatment of stomach-related diseases and personalized medicine.
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Affiliation(s)
- Yi-Yang Liu
- Graduate School, Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
| | - De-Kun Wu
- Teaching Experiment and Training Center, Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
| | - Ji-Bing Chen
- Central Laboratory, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
| | - You-Ming Tang
- Department of Digestive Disease, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
| | - Feng Jiang
- AIDS Research Center, Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
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Taverna JA, Hung CN, Williams M, Williams R, Chen M, Kamali S, Sambandam V, Hsiang-Ling Chiu C, Osmulski PA, Gaczynska ME, DeArmond DT, Gaspard C, Mancini M, Kusi M, Pandya AN, Song L, Jin L, Schiavini P, Chen CL. Ex vivo drug testing of patient-derived lung organoids to predict treatment responses for personalized medicine. Lung Cancer 2024; 190:107533. [PMID: 38520909 PMCID: PMC12045304 DOI: 10.1016/j.lungcan.2024.107533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 03/06/2024] [Accepted: 03/07/2024] [Indexed: 03/25/2024]
Abstract
Lung cancer is the leading cause of global cancer-related mortality resulting in ∼ 1.8 million deaths annually. Systemic, molecular targeted, and immune therapies have provided significant improvements of survival outcomes for patients. However, drug resistance usually arises and there is an urgent need for novel therapy screening and personalized medicine. 3D patient-derived organoid (PDO) models have emerged as a more effective and efficient alternative for ex vivo drug screening than 2D cell culture and patient-derived xenograft (PDX) models. In this review, we performed an extensive search of lung cancer PDO-based ex vivo drug screening studies. Lung cancer PDOs were successfully established from fresh or bio-banked sections and/or biopsies, pleural effusions and PDX mouse models. PDOs were subject to ex vivo drug screening with chemotherapy, targeted therapy and/or immunotherapy. PDOs consistently recapitulated the genomic alterations and drug sensitivity of primary tumors. Although sample sizes of the previous studies were limited and some technical challenges remain, PDOs showed great promise in the screening of novel therapy drugs. With the technical advances of high throughput, tumor-on-chip, and combined microenvironment, the drug screening process using PDOs will enhance precision care of lung cancer patients.
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Affiliation(s)
- Josephine A Taverna
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Department of Medicine, Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX, USA.
| | - Chia-Nung Hung
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA
| | - Madison Williams
- Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Department of Medicine, Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX, USA; Department of General Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ryan Williams
- Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Department of Medicine, Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX, USA; Department of General Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Meizhen Chen
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA
| | | | | | - Cheryl Hsiang-Ling Chiu
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA
| | - Pawel A Osmulski
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA
| | - Maria E Gaczynska
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA
| | - Daniel T DeArmond
- Department of Medicine, Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX, USA; Department of General Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Cardiothoracic Surgery, University of Texas Health Science Center, San Antonio, Texas and Department of Laboratory Medicine, Baptist Health System, San Antonio, TX, USA
| | - Christine Gaspard
- Dolph Briscoe, Jr. Library, University of Texas Health Science Center, San Antonio, TX, USA
| | | | - Meena Kusi
- Deciphera Pharmaceuticals, LLC., Waltham, MA, USA
| | - Abhishek N Pandya
- Department of Medicine, Division of Hematology and Oncology, University of Texas Health Science Center, San Antonio, TX, USA
| | - Lina Song
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA
| | - Lingtao Jin
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA
| | | | - Chun-Liang Chen
- Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; School of Nursing, University of Texas Health Science Center, San Antonio, TX, USA.
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Qi H, Tan X, Zhang W, Zhou Y, Chen S, Zha D, Wang S, Wen J. The applications and techniques of organoids in head and neck cancer therapy. Front Oncol 2023; 13:1191614. [PMID: 37427120 PMCID: PMC10328716 DOI: 10.3389/fonc.2023.1191614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 06/09/2023] [Indexed: 07/11/2023] Open
Abstract
Head and neck cancer (HNC) is one of the most common cancers on the planet, with approximately 600,000 new cases diagnosed and 300,000 deaths every year. Research into the biological basis of HNC has advanced slowly over the past decades, which has made it difficult to develop new, more effective treatments. The patient-derived organoids (PDOs) are made from patient tumor cells, resembling the features of their tumors, which are high-fidelity models for studying cancer biology and designing new precision medicine therapies. In recent years, considerable effort has been focused on improving "organoids" technologies and identifying tumor-specific medicine using head and neck samples and a variety of organoids. A review of improved techniques and conclusions reported in publications describing the application of these techniques to HNC organoids is presented here. Additionally, we discuss the potential application of organoids in head and neck cancer research as well as the limitations associated with these models. As a result of the integration of organoid models into future precision medicine research and therapeutic profiling programs, the use of organoids will be extremely significant in the future.
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Affiliation(s)
- Hao Qi
- The Cancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Xiaolin Tan
- The Cancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Department of Clinical Nutrition, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Wenshuo Zhang
- Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yihong Zhou
- Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Shaoyi Chen
- The Cancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Dasong Zha
- The Cancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Siyang Wang
- The Cancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Jinming Wen
- The Cancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
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Farshbaf A, Lotfi M, Zare R, Mohtasham N. The organoid as reliable cancer modeling in personalized medicine, does applicable in precision medicine of head and neck squamous cell carcinoma? THE PHARMACOGENOMICS JOURNAL 2022; 23:37-44. [PMID: 36347937 DOI: 10.1038/s41397-022-00296-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 10/22/2022] [Accepted: 10/31/2022] [Indexed: 11/09/2022]
Abstract
Head and neck squamous cell carcinomas (HNSCCs) are introduced as the sixth most common cancer in the world. Detection of predictive biomarkers improve early diagnosis and prognosis. Recent cancer researches provide a new avenue for organoids, known as "mini-organs" in a dish, such as patient-derived organoids (PDOs), for cancer modeling. HNSCC burden, heterogeneity, mutations, and organoid give opportunities for the evaluation of drug sensitivity/resistance response according to the unique genetic profile signature. The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) nucleases, as an efficient genome engineering technology, can be used for genetic manipulation in three-dimensional (3D) organoids for cancer modeling by targeting oncogenes/tumor suppressor genes. Moreover, single-cell analysis of circulating tumor cells (CTCs) improved understanding of molecular angiogenesis, distance metastasis, and drug screening without the need for tissue biopsy. Organoids allow us to investigate the biopathogenesis of cancer, tumor cell behavior, and drug screening in a living biobank according to the specific genetic profile of patients.
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Kumari R, Xu X, Li HQX. Translational and Clinical Relevance of PDX-Derived Organoid Models in Oncology Drug Discovery and Development. Curr Protoc 2022; 2:e431. [PMID: 35789132 DOI: 10.1002/cpz1.431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Patient-derived cancer disease models conserve many key features of the original human cancers, potentially allowing higher predictive power than traditional cell line models. Accordingly, in vivo patient-derived xenografts (PDX) are frequently utilized in preclinical and translational oncology studies as patient surrogates for population-based screens ("mouse clinical trials"), for which large PDX biobanks have been generated over the last decade from various cancer types. In vitro patient-derived organoids (PDO) have recently emerged as a disruptive technology, enabling early "patient in a dish" clinical trials. Like PDX, PDOs retain the histology/genomics of the original tumor and are highly predictive of the clinical response. Organoids derived from adult stem cells (ASC) in patient tissue can function as mini-organs. They have greater advantages over other 3D in vitro systems, making them highly predictive, reliable, and consistent in vitro models. Large biobanks enable the adoption of organoids in early drug screening and patient selection. PDX biobanks, as a source of human material, have been used to create 3D in vitro screens, but with limitations. However, creating organoids from the ASCs residing in PDXs has been successfully used as a rapid and cost-effective way to enable higher throughput in vitro screens and generate matched in vitro/in vivo model pairs that retain genomic, histopathological, and pharmacology profiles. This overview summarizes the generation of matched in vitro/in vivo models from patient material, the advantages over other systems, and the applications to drug discovery. © 2022 Wiley Periodicals LLC.
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Affiliation(s)
| | - Xiaoxi Xu
- Crown Bioscience Inc., Beijing, China
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Wang Y, Li Y, Sheng Z, Deng W, Yuan H, Wang S, Liu Y. Advances of Patient-Derived Organoids in Personalized Radiotherapy. Front Oncol 2022; 12:888416. [PMID: 35574360 PMCID: PMC9102799 DOI: 10.3389/fonc.2022.888416] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 03/28/2022] [Indexed: 11/16/2022] Open
Abstract
Patient-derived organoids (PDO), based on the advanced three-dimensional (3D) culture technology, can provide more relevant physiological and pathological cancer models, which is especially beneficial for developing and optimizing cancer therapeutic strategies. Radiotherapy (RT) is a cornerstone of curative and palliative cancer treatment, which can be performed alone or integrated with surgery, chemotherapy, immunotherapy, or targeted therapy in clinical care. Among all cancer therapies, RT has great local control, safety and effectiveness, and is also cost-effective per life-year gained for patients. It has been reported that combing RT with chemotherapy or immunotherapy or radiosensitizer drugs may enhance treatment efficacy at faster rates and lower cost. However, very few FDA-approved combinations of RT with drugs or radiosensitizers exist due to the lack of accurate and relevant preclinical models. Meanwhile, radiation dose escalation may increase treatment efficacy and induce more toxicity of normal tissue as well, which has been studied by conducting various clinical trials, very expensive and time-consuming, often burdensome on patients and sometimes with controversial results. The surged PDO technology may help with the preclinical test of RT combination and radiation dose escalation to promote precision radiation oncology, where PDO can recapitulate individual patient’ tumor heterogeneity, retain characteristics of the original tumor, and predict treatment response. This review aims to introduce recent advances in the PDO technology and personalized radiotherapy, highlight the strengths and weaknesses of the PDO cancer models, and finally examine the existing RT-related PDO trials or applications to harness personalized and precision radiotherapy.
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Affiliation(s)
- Yuenan Wang
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Shenzhen, China
- *Correspondence: Yuenan Wang, ; Yajie Liu, ; Shubin Wang,
| | - Ye Li
- Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Zonghai Sheng
- Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Weiwei Deng
- Department of Mechanical and Aerospace Engineering, Southern University of Science and Technology, Shenzhen, China
| | - Hongyan Yuan
- Department of Mechanical and Aerospace Engineering, Southern University of Science and Technology, Shenzhen, China
| | - Shubin Wang
- Department of Medical Oncology, Peking University Shenzhen Hospital, Shenzhen, China
- *Correspondence: Yuenan Wang, ; Yajie Liu, ; Shubin Wang,
| | - Yajie Liu
- Department of Radiation Oncology, Peking University Shenzhen Hospital, Shenzhen, China
- *Correspondence: Yuenan Wang, ; Yajie Liu, ; Shubin Wang,
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Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves' hyperthyroidism. Proc Natl Acad Sci U S A 2021; 118:2117017118. [PMID: 34916298 PMCID: PMC8713972 DOI: 10.1073/pnas.2117017118] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/11/2021] [Indexed: 12/16/2022] Open
Abstract
The thyroid is essential for maintaining systemic homeostasis by regulating thyroid hormone concentrations in the bloodstream. This study describes an organoid-based model system to study mouse and human thyroid biology. Moreover, the study explores the potential of human organoids for modeling autoimmune disease, the anti-TSH receptor (TSHR) antibody-driven Graves’ hyperthyroidism. The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of three-dimensional (3D) organoids from adult thyroid tissue representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCOs) harbor the complete machinery of hormone production as visualized by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarized epithelial cells that surround a central lumen. Both the established murine as human thyroid organoids express canonical thyroid markers PAX8 and NKX2.1, while the thyroid hormone precursor thyroglobulin is expressed at comparable levels to tissue. Single-cell RNA sequencing and transmission electron microscopy confirm that TFCOs phenocopy primary thyroid tissue. Thyroid hormones are readily detectable in conditioned medium of human TFCOs. We show clinically relevant responses (increased proliferation and hormone secretion) of human TFCOs toward a panel of Graves’ disease patient sera, demonstrating that organoids can model human autoimmune disease.
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