Yingjuan Liu, Honglin Xu, S. Abraham, X. Wang, B. Keavney
Review Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models Yingjuan Liu *, Honglin Xu, Sabu Abraham, Xin Wang, and Bernard D. Keavney* Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT, UK. * Correspondence: yingjuan.liu@manchester.ac.uk (Yingjuan Liu); bernard.keavney@manchester.ac.uk (Bernard D. Keavney) Received: 1 November 2022 Accepted: 24 November 2022 Published: 21 December 2022 Abstract: Currently, with an increased requirement for new therapeutic strategies, preclinical drug testing or screening platforms have rapidly evolved in recent years. In comparison to traditional 2D cell cultures, 3D organoids or spheroids with or without scaffolds improve the microenvironment of in vitro cultures, advancing the in vitro biological observation and enabling mechanistic studies of drug reactions in the human tissue-like environment. 3D organoids and spheroids are straightforward to produce, and relatively uniform in size and shape. This helps to facilitate high throughput screening requirements. Spheroids and organoids have been applied in anti-cancer drug testing, toxicity evaluations, as well as mechanism studies for variable organ systems, including the intestine, liver, pancreas, brain, and heart. Among 3D cultures of spheroids and organoids, ‘tumour spheroids’ formed by dissociated tumour tissues or cancer cell lines are relatively simple in composition and commonly applied to anticancer drug screening. The ‘healthy organoids’ differentiated from hiPSCs/hESCs are more complex in cell composition, distribution, structure and function with higher similarity to in vivo organs, and have found applications in toxicity tests, personalised medicine, and therapeutic and mechanistic studies. In most cases, the multicellular 3D organoids are more resistant and stable in reaction to stimulations or chemicals in vitro , suggesting more accurate modelling of in vivo responses. Here, we review recent progress in human-origin organoid/spheroid systems and their applications in preclinical studies.
刘颖娟*，徐宏林，Sabu Abraham，王鑫，Bernard D. Keavney*英国曼彻斯特大学生物医学与健康学院心血管科学部，M13 9PT，英国。*通讯:yingjuan.liu@manchester.ac.uk (Yingjuan Liu);bernard.keavney@manchester.ac.uk (Bernard D. Keavney)收稿日期:2022年11月1日接收日期:2022年11月24日发布日期:2022年12月21日摘要:目前，随着对新的治疗策略的需求增加，临床前药物测试或筛选平台近年来迅速发展。与传统的二维细胞培养相比，有或无支架的三维类器官或球体改善了体外培养的微环境，推进了体外生物学观察，使药物在人体类组织环境中的反应机理研究成为可能。3D类器官和球体的制作很简单，尺寸和形状也相对统一。这有助于促进高通量筛选要求。球体和类器官已被应用于抗癌药物测试、毒性评估以及各种器官系统的机制研究，包括肠、肝、胰腺、脑和心脏。在球体和类器官的三维培养中，由游离的肿瘤组织或癌细胞系形成的“肿瘤球体”成分相对简单，通常用于抗癌药物筛选。从hiPSCs/hESCs分化出来的“健康类器官”在细胞组成、分布、结构和功能上更复杂，与体内器官具有更高的相似性，并已在毒性测试、个性化药物以及治疗和机制研究中得到应用。在大多数情况下，多细胞3D类器官在体外对刺激或化学物质的反应更有抵抗力和稳定性，这表明更准确的体内反应建模。在此，我们综述了人类来源的类器官/球体系统及其在临床前研究中的应用的最新进展。
{"title":"Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models","authors":"Yingjuan Liu, Honglin Xu, S. Abraham, X. Wang, B. Keavney","doi":"10.53941/ijddp.v1i1.188","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.188","url":null,"abstract":"Review\u0000Progress of 3D Organoid Technology for Preclinical Investigations: Towards Human In Vitro Models\u0000\u0000Yingjuan Liu *, Honglin Xu, Sabu Abraham, Xin Wang, and Bernard D. Keavney*\u0000\u0000\u0000Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT, UK.\u0000* Correspondence: yingjuan.liu@manchester.ac.uk (Yingjuan Liu);\u0000bernard.keavney@manchester.ac.uk (Bernard D. Keavney)\u0000 \u0000 \u0000Received: 1 November 2022\u0000Accepted: 24 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Currently, with an increased requirement for new therapeutic strategies, preclinical drug testing or screening platforms have rapidly evolved in recent years. In comparison to traditional 2D cell cultures, 3D organoids or spheroids with or without scaffolds improve the microenvironment of in vitro cultures, advancing the in vitro biological observation and enabling mechanistic studies of drug reactions in the human tissue-like environment. 3D organoids and spheroids are straightforward to produce, and relatively uniform in size and shape. This helps to facilitate high throughput screening requirements. Spheroids and organoids have been applied in anti-cancer drug testing, toxicity evaluations, as well as mechanism studies for variable organ systems, including the intestine, liver, pancreas, brain, and heart. Among 3D cultures of spheroids and organoids, ‘tumour spheroids’ formed by dissociated tumour tissues or cancer cell lines are relatively simple in composition and commonly applied to anticancer drug screening. The ‘healthy organoids’ differentiated from hiPSCs/hESCs are more complex in cell composition, distribution, structure and function with higher similarity to in vivo organs, and have found applications in toxicity tests, personalised medicine, and therapeutic and mechanistic studies. In most cases, the multicellular 3D organoids are more resistant and stable in reaction to stimulations or chemicals in vitro , suggesting more accurate modelling of in vivo responses. Here, we review recent progress in human-origin organoid/spheroid systems and their applications in preclinical studies.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83743757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shou-bao Wang, Zihan Wang, Lianhua Fang, Yang Lv, G. Du
Review Advances of the Target-Based and Phenotypic Screenings and Strategies in Drug Discovery Shoubao Wang 1,*, Zihan Wang1, Lianhua Fang1, Yang Lv2, and Guanhua Du1,* 1 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. 2 Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. * Correspondence: shoubaowang@imm.ac.cn (Shoubao Wang); dugh@imm.ac.cn (Guanhua Du). Received: 8 November 2022 Accepted: 15 November 2022 Published: 21 December 2022 Abstract: Drug discovery and development is a complex and expensive process. There are two approaches, phenotypic and target-based approaches, each holding different advantages for screening novel drug candidates when pursuing successful marketing authorization. However, the attrition rates of drug candidates continue to increase. In this review, we discuss recent successes and ongoing advances in phenotypic screening and target-based screening for drug discovery. We also explore how strategic and technological innovations may fuel new approaches in drug discovery. There are two approaches in drug discovery.
{"title":"Advances of the Target-Based and Phenotypic Screenings and Strategies in Drug Discovery","authors":"Shou-bao Wang, Zihan Wang, Lianhua Fang, Yang Lv, G. Du","doi":"10.53941/ijddp.v1i1.199","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.199","url":null,"abstract":"Review\u0000Advances of the Target-Based and Phenotypic Screenings and Strategies in Drug Discovery\u0000\u0000Shoubao Wang 1,*, Zihan Wang1, Lianhua Fang1, Yang Lv2, and Guanhua Du1,*\u0000\u0000\u00001 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.\u00002 Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.\u0000* Correspondence: shoubaowang@imm.ac.cn (Shoubao Wang); dugh@imm.ac.cn (Guanhua Du).\u0000 \u0000 \u0000Received: 8 November 2022\u0000Accepted: 15 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Drug discovery and development is a complex and expensive process. There are two approaches, phenotypic and target-based approaches, each holding different advantages for screening novel drug candidates when pursuing successful marketing authorization. However, the attrition rates of drug candidates continue to increase. In this review, we discuss recent successes and ongoing advances in phenotypic screening and target-based screening for drug discovery. We also explore how strategic and technological innovations may fuel new approaches in drug discovery. There are two approaches in drug discovery.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82225834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Review From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia Yufei Zhou and Chen Chen * Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. * Correspondence: chenchen@tjh.tjmu.edu.cn; Tel. & Fax: 86-27-6937-8422. Received: 7 October 2022 Accepted: 1 November 2022 Published: 21 December 2022 Abstract: Hyperlipidemia is one of the conditions that constitute metabolic disorder and it is a common public health problem. The condition is characterized by increased levels of cholesterol, triglycerides and/or lipoproteins; it is a recognized as a risk factor for the onset of many diseases such as type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Up to now, the primary drugs for treating hyperlipidemia are statins and monoclonal antibody drugs against proprotein convertase subtilisin/kexin type 9 (PCSK9). The main limitation of statins for long-term use is intolerable side effects. Evolocumab and Alirocumab, two monoclonal antibodies against PCSK9, can effectively decrease the level of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance and familial hypercholesterolemia, while causing fewer side effects. However, due to its short half-life and high costs, these monoclonal antibody treatments might result in patients’ non-compliance with medication and considerable economic burden on patients. Given that RNA plays a key role in gene regulation, RNA-based therapeutics have become powerful blueprints for designing new anti-hyperlipidemia drugs. Here, we summarized RNA-based therapeutic strategies and the current clinical trials for RNA drugs in hyperlipidemia treatment.
{"title":"From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia","authors":"Yufei Zhou, Chen Chen","doi":"10.53941/ijddp.v1i1.141","DOIUrl":"https://doi.org/10.53941/ijddp.v1i1.141","url":null,"abstract":"Review\u0000From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia\u0000\u0000Yufei Zhou and Chen Chen *\u0000\u0000\u0000Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.\u0000* Correspondence: chenchen@tjh.tjmu.edu.cn; Tel. & Fax: 86-27-6937-8422.\u0000 \u0000 \u0000Received: 7 October 2022\u0000Accepted: 1 November 2022\u0000Published: 21 December 2022\u0000 \u0000\u0000Abstract: Hyperlipidemia is one of the conditions that constitute metabolic disorder and it is a common public health problem. The condition is characterized by increased levels of cholesterol, triglycerides and/or lipoproteins; it is a recognized as a risk factor for the onset of many diseases such as type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Up to now, the primary drugs for treating hyperlipidemia are statins and monoclonal antibody drugs against proprotein convertase subtilisin/kexin type 9 (PCSK9). The main limitation of statins for long-term use is intolerable side effects. Evolocumab and Alirocumab, two monoclonal antibodies against PCSK9, can effectively decrease the level of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance and familial hypercholesterolemia, while causing fewer side effects. However, due to its short half-life and high costs, these monoclonal antibody treatments might result in patients’ non-compliance with medication and considerable economic burden on patients. Given that RNA plays a key role in gene regulation, RNA-based therapeutics have become powerful blueprints for designing new anti-hyperlipidemia drugs. Here, we summarized RNA-based therapeutic strategies and the current clinical trials for RNA drugs in hyperlipidemia treatment.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81076074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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