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中国生物工程杂志

China Biotechnology
China Biotechnology
China Biotechnology  2023, Vol. 43 Issue (8): 1-10    DOI: 10.13523/j.cb.2302013
    
Development Status and Prospects of Organoids
WANG Yue,SHI Hui-lin,JIN Chen-qi,XU Ping**()
Shanghai Information Center for Life Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200031, China
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Abstract  

The emergence and rapid development of the organoid technology has greatly improved the manufacturing ability of artificial tissues and organs, expanded the application scope of regenerative medicine, and also brought new opportunities for the development of the biomedicine industry. The analysis of the development status of the organoid technology, its application direction and industry development shows that this field is in a period of rapid growth. First, the organoid technology is in a period of explosive growth at present, the simulation level of structure and function of tissues and organs is constantly improved, and breakthroughs have been made in solving core “bottleneck” problems such as vascularization. Second, the organoids-on-a-chip technology produced by the fusion of the organoid technology and organ-on-a-chip has greatly improved the application ability of organoids. Finally, as a biological model, organoids have shown considerable application prospects in biomedical research, clinical treatment and drug research and development. Especially in drug research and development, the relevant industrial system is gradually taking shape, and the development process is advancing rapidly. In the future, with breakthoughs made in overcoming relevant technical bottlenecks and the further influx of commercial capital, the field of organoids will certainly have a broader development space, which will help the innovation and development of the biomedicine industry.

Key words： Organoid      Regenerative      medicine      Biological      model      Medicine      development     
Received: 09 February 2023      Published: 05 September 2023
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Yue WANG
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Cite this article:

WANG Yue, SHI Hui-lin, JIN Chen-qi, XU Ping. Development Status and Prospects of Organoids. China Biotechnology, 2023, 43(8): 1-10.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.2302013     OR     https://manu60.magtech.com.cn/biotech/Y2023/V43/I8/1

Fig.1 Annual distribution of global organoid papers Source of data:ISI Science Citation Index Expanded
Fig.2 The main application scenarios of organoids
药物企业 类器官企业 合作事项 时间
阿斯利康 Emulate 类器官芯片技术嵌入到阿斯利康的IMED药物安全实验室中 2018年
辉瑞 Hubrecht Organoid Technology 合作开发人类肠道类器官平台,用于克罗恩病、溃疡性结肠炎的
药物靶标识别和药物筛选		 2018年
辉瑞 System1 Biosciences 辉瑞领投,开发大脑类器官 2018年
赛诺菲 Hesperos NCT04658472临床前研究 2021年
Crown Bioscience Crown Bioscience 利用类器官平台对细胞药物进行筛选和表征 2022年
百时美施贵宝 Prellis 基于其人体淋巴结类器官,开发针对人类蛋白质的高亲和力人类抗体 2022年
赛诺菲 Prellis 利用其淋巴结类器官,在体外重建免疫反应,以助力抗体药物的开发 2022年
Table 1 Case of cooperation between drug R&D companies and organoid companies
公司名称 融资情况 融资时间 研发方向
丹望医疗 1.2亿元A轮融资 2021年 专注类器官疾病模型的平台型公司
创芯国际 1亿元 pre-B轮融资 2022年 提供科研与临床精准治疗的肿瘤类器官药物敏感性检测平台、新药研发服务
大橡科技 近亿元pre-B轮融资 2022年 类器官芯片在新药研发、疾病建模和个体化精准医疗等领域的广泛应用
科途医学 数千万A轮融资 2022年 专注于肿瘤类器官功能性检测技术的研发和成果转化
艾玮得生物 近亿元pre-A轮融资 2022年 重点从事人体器官芯片及配套装备的研发和应用
伯桢生物 亿元A轮融资 2023年 类器官自动化设备、多组织全流程试剂盒、类器官培养和样本库构建技术
方案、类器官药物研发和精准医疗子系统等
Table 2 Financing situation of some organoids R&D companies in China
[1]   Nature Methods. Method of the year 2017: organoids. Nature Methods, 2018, 15(1): 1.
doi: 10.1038/nmeth.4575
[2]   Sato T, Vries R G, Snippert H J, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 2009, 459(7244): 262-265.
doi: 10.1038/nature07935
[3]   Takebe T, Sekine K, Enomura M, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature, 2013, 499(7459): 481-484.
doi: 10.1038/nature12271
[4]   Xia Y, Nivet E, Sancho-Martinez I, et al. Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nature Cell Biology, 2013, 15(12): 1507-1515.
doi: 10.1038/ncb2872 pmid: 24240476
[5]   Lancaster M A, Renner M, Martin C A, et al. Cerebral organoids model human brain development and microcephaly. Nature, 2013, 501(7467): 373-379.
doi: 10.1038/nature12517
[6]   Dishing up mini-organs. Science, 2013, 342(6165): 1436-1437.
[7]   Chen Y W, Huang S X, de Carvalho A L R T, et al. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nature Cell Biology, 2017, 19(5): 542-549.
doi: 10.1038/ncb3510
[8]   McCracken K W, Catá E M, Crawford C M, et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature, 2014, 516(7531): 400-404.
doi: 10.1038/nature13863
[9]   Nakano T, Ando S, Takata N, et al. Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell, 2012, 10(6): 771-785.
doi: S1934-5909(12)00242-1 pmid: 22704518
[10]   Kessler M, Hoffmann K, Brinkmann V, et al. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nature Communications, 2015, 6(1): 1-11.
[11]   Wimmer R A, Leopoldi A, Aichinger M, et al. Human blood vessel organoids as a model of diabetic vasculopathy. Nature, 2019, 565(7740): 505-510.
doi: 10.1038/s41586-018-0858-8
[12]   Georgakopoulos N, Prior N, Angres B, et al. Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids. BMC Developmental Biology, 2020, 20(1): 4.
doi: 10.1186/s12861-020-0209-5 pmid: 32098630
[13]   Lee J, Rabbani C C, Gao H, et al. Organoid cultures derived from patients with advanced prostate cancer. Nature, 2020, 582: 399-404.
doi: 10.1038/s41586-020-2352-3
[14]   Drakhlis L, Biswanath S, Farr C M, et al. Human heart-forming organoids recapitulate early heart and foregut development. Nature Biotechnology, 2021, 39(6): 737-746.
doi: 10.1038/s41587-021-00815-9 pmid: 33558697
[15]   Basak O, Beumer J, Wiebrands K, et al. Induced quiescence of Lgr5+ stem cells in intestinal organoids enables differentiation of hormone-producing enteroendocrine cells. Cell Stem Cell, 2017, 20(2): 177-190.e4.
doi: S1934-5909(16)30397-6 pmid: 27939219
[16]   Bouffi C, Wikenheiser-Brokamp K A, Chaturvedi P, et al. In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice. Nature Biotechnology, 2023, 41(6): 824-831.
doi: 10.1038/s41587-022-01558-x pmid: 36702898
[17]   庞溦, 刘彦彤, 向阳飞. 脑类器官技术研究进展. 中国科学(生命科学), 2023, 53(2): 161-174.
[17]   Pang W, Liu Y T, Xiang Y F. Current progress in brain organoid technology. Scientia Sinica (Vitae), 2023, 53(2): 161-174.
[18]   Lu X X, Yang J J, Xiang Y F. Modeling human neurodevelopmental diseases with brain organoids. Cell Regeneration (London, England), 2022, 11(1): 1.
[19]   Revah O, Gore F, Kelley K W, et al. Maturation and circuit integration of transplanted human cortical organoids. Nature, 2022, 610(7931): 319-326.
doi: 10.1038/s41586-022-05277-w
[20]   许耿, 顾海涛. 心脏类器官的研究进展及其临床应用. 南京医科大学学报(自然科学版), 2021, 41(12): 1837-1842.
[20]   Xu G, Gu H T. Advances in research and application of cardiac organoids. Journal of Nanjing Medical University (Natural Sciences), 2021, 41(12): 1837-1842.
[21]   Hofbauer P, Jahnel S M, Papai N, et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell, 2021, 184(12): 3299-3317.e22.
doi: 10.1016/j.cell.2021.04.034 pmid: 34019794
[22]   Pham M T, Pollock K M, Rose M D, et al. Generation of human vascularized brain organoids. Neuroreport, 2018, 29(7): 588-593.
doi: 10.1097/WNR.0000000000001014 pmid: 29570159
[23]   Cakir B, Xiang Y F, Tanaka Y, et al. Engineering of human brain organoids with a functional vascular-like system. Nature Methods, 2019, 16(11): 1169-1175.
doi: 10.1038/s41592-019-0586-5 pmid: 31591580
[24]   Shi Y C, Sun L, Wang M D, et al. Vascularized human cortical organoids (vOrganoids) model cortical development in vivo. PLoS Biology, 2020, 18(5): e3000705.
[25]   Holloway E M, Wu J H, Czerwinski M, et al. Differentiation of human intestinal organoids with endogenous vascular endothelial cells. Developmental Cell, 2020, 54(4): 516-528.e7.
doi: S1534-5807(20)30598-0 pmid: 32841595
[26]   Drakhlis L, Biswanath S, Farr C M, et al. Human heart-forming organoids recapitulate early heart and foregut development. Nature Biotechnology, 2021, 39(6): 737-746.
doi: 10.1038/s41587-021-00815-9 pmid: 33558697
[27]   Low J H, Li P, Chew E G Y, et al. Generation of human PSC-derived kidney organoids with patterned nephron segments and a de novo vascular network. Cell Stem Cell, 2019, 25(3): 373-387.e9.
doi: 10.1016/j.stem.2019.06.009
[28]   Chen X W, Sun G Q, Tian E, et al. Modeling sporadic alzheimer’s disease in human brain organoids under serum exposure. Advanced Science, 2021, 8(18): 2101462.
[29]   Jo J, Yang L, Tran H D, et al. Lewy body-like inclusions in human midbrain organoids carrying glucocerebrosidase and α-synuclein mutations. Annals of Neurology, 2021, 90(3): 490-505.
doi: 10.1002/ana.v90.3
[30]   Suzuki K, Murano T, Shimizu H, et al. Single cell analysis of Crohn’s disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties. Journal of Gastroenterology, 2018, 53(9): 1035-1047.
doi: 10.1007/s00535-018-1437-3 pmid: 29374777
[31]   Sarvestani S K, Signs S, Hu B, et al. Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity. Nature Communications, 2021, 12(1): 1-18.
doi: 10.1038/s41467-020-20314-w
[32]   Gao D, Vela I, Sboner A, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell, 2014, 159(1): 176-187.
doi: S0092-8674(14)01047-2 pmid: 25201530
[33]   Neal J T, Li X N, Zhu J J, et al. Organoid modeling of the tumor immune microenvironment. Cell, 2018, 175(7): 1972-1988.e16.
doi: S0092-8674(18)31513-7 pmid: 30550791
[34]   Koike H, Iwasawa K, Ouchi R E, et al. Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary. Nature, 2019, 574(7776): 112-116.
doi: 10.1038/s41586-019-1598-0
[35]   Gabriel E, Albanna W, Pasquini G, et al. Human brain organoids assemble functionally integrated bilateral optic vesicles. Cell Stem Cell, 2021, 28(10): 1740-1757.e8.
doi: 10.1016/j.stem.2021.07.010 pmid: 34407456
[36]   Amadei G, Handford C E, Qiu C X, et al. Embryo model completes gastrulation to neurulation and organogenesis. Nature, 2022, 610(7930): 143-153.
doi: 10.1038/s41586-022-05246-3
[37]   Kim E, Choi S, Kang B, et al. Creation of bladder assembloids mimicking tissue regeneration and cancer. Nature, 2020, 588(7839): 664-669.
doi: 10.1038/s41586-020-3034-x
[38]   Andersen J, Revah O, Miura Y, et al. Generation of functional human 3D cortico-motor assembloids. Cell, 2020, 183(7): 1913-1929.e26.
doi: 10.1016/j.cell.2020.11.017 pmid: 33333020
[39]   Mansour A A, Gonçalves J T, Bloyd C W, et al. An in vivo model of functional and vascularized human brain organoids. Nature Biotechnology, 2018, 36(5): 432-441.
doi: 10.1038/nbt.4127
[40]   Takeishi K, de l’Hortet A C, Wang Y, et al. Assembly and function of a bioengineered human liver for transplantation generated solely from induced pluripotent stem cells. Cell Reports, 2020, 31(9): 107711.
doi: 10.1016/j.celrep.2020.107711
[41]   Sampaziotis F, Muraro D, Tysoe O C, et al. Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science, 2021, 371(6531): 839-846.
doi: 10.1126/science.aaz6964 pmid: 33602855
[42]   Fleck J S, Jansen S M J, Wollny D, et al. Inferring and perturbing cell fate regulomes in human brain organoids. Nature, 2022: 1-8.
[43]   Liu X D, Tan J P, Schröder J, et al. Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature, 2021, 591(7851): 627-632.
doi: 10.1038/s41586-021-03372-y
[44]   Moris N, Anlas K, van den Brink S C, et al. An in vitro model of early anteroposterior organization during human development. Nature, 2020, 582(7812): 410-415.
doi: 10.1038/s41586-020-2383-9
[45]   Yu L Q, Wei Y L, Duan J L, et al. Blastocyst-like structures generated from human pluripotent stem cells. Nature, 2021, 591(7851): 620-626.
doi: 10.1038/s41586-021-03356-y
[46]   Hendriks D, Brouwers J F, Hamer K, et al. Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis. Nature Biotechnology, 2023, 1-15. DOI: org/10.1038/s41587-023-01680-4
doi: org/10.1038/s41587-023-01680-4
[47]   Zhao Y, Li Z X, Zhu Y J, et al. Single-cell transcriptome analysis uncovers intratumoral heterogeneity and underlying mechanisms for drug resistance in hepatobiliary tumor organoids. Advanced Science, 2021, 8(11): 2003897.
[48]   van Neerven S M, de Groot N E, Nijman L E, et al. Apc-mutant cells act as supercompetitors in intestinal tumour initiation. Nature, 2021, 594(7863): 436-441.
doi: 10.1038/s41586-021-03558-4
[49]   Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science, 2018, 359(6378): 920-926.
doi: 10.1126/science.aao2774 pmid: 29472484
[50]   Wang H M, Zhang C Y, Peng K C, et al. Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: a real-world study. Cell Reports Medicine, 2023, 4(2): 100911.
doi: 10.1016/j.xcrm.2022.100911
[51]   Tran T, Song C J, Nguyen T, et al. A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery. Cell Stem Cell, 2022, 29(7): 1083-1101.e7.
doi: 10.1016/j.stem.2022.06.005 pmid: 35803227
[52]   杨换连, 邱飞, 王国权, 等. 肿瘤类器官在药物筛选和个性化用药中的研究进展. 中国生物工程杂志, 2022, 42(6): 47-53.
[52]   Yang H L, Qiu F, Wang G Q, et al. Progress in the research and application of tumor organoids in drug screening and personalized drug treatment. China Biotechnology, 2022, 42(6): 47-53.
[53]   Wang D S, Wang J Q, Bai L Y, et al. Long-term expansion of pancreatic islet organoids from resident procr+ progenitors. Cell, 2020, 180(6): 1198-1211.e19.
doi: 10.1016/j.cell.2020.02.048
[54]   Wang J Q, Wang D S, Chen X Y, et al. Isolation of mouse pancreatic islet Procr+ progenitors and long-term expansion of islet organoids in vitro. Nature Protocols, 2022, 17(5): 1359-1384.
doi: 10.1038/s41596-022-00683-w
[55]   Sun L L, Wang Y Q, Cen J, et al. Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes. Nature Cell Biology, 2019, 21(8): 1015-1026.
doi: 10.1038/s41556-019-0359-5 pmid: 31332348
[56]   Tao T T, Deng P W, Wang Y Q, et al. Microengineered multi-organoid system from hiPSCs to recapitulate human liver-islet axis in normal and type 2 diabetes. Advanced Science, 2022, 9(5): 2103495.
[57]   Xie C, Liang R J, Ye J C, et al. High-efficient engineering of osteo-callus organoids for rapid bone regeneration within one month. Biomaterials, 2022, 288: 121741.
doi: 10.1016/j.biomaterials.2022.121741
[58]   Zhao B, Ni C, Gao R, et al. Recapitulation of SARS-CoV-2 infection and cholangiocyte damage with human liver ductal organoids. Protein & Cell, 2020, 11(10): 771-775.
[59]   Han Y L, Duan X H, Yang L L, et al. Identification of SARS-CoV-2 inhibitors using lung and colonic organoids. Nature, 2021, 589(7841): 270-275.
doi: 10.1038/s41586-020-2901-9
[60]   Jiang S W, Zhao H R, Zhang W J, et al. An automated organoid platform with inter-organoid homogeneity and inter-patient heterogeneity. Cell Reports Medicine, 2020, 1(9): 100161.
doi: 10.1016/j.xcrm.2020.100161
[61]   Qu M L, Xiong L, Lyu Y L, et al. Establishment of intestinal organoid cultures modeling injury-associated epithelial regeneration. Cell Research, 2021, 31(3): 259-271.
doi: 10.1038/s41422-020-00453-x pmid: 33420425
[62]   冯紫伊, 梁珊珊, 于炜婷, 等. 患者来源肿瘤类器官的培养与研究及应用. 中国组织工程研究, 2021, 25(25): 4082-4088.
[62]   Feng Z, Liang S, Yu W, et al. Culture, research and application of patient-derived tumor organoids. Chinese Journal of Tissue Engineering Research, 2021, 25(25): 4082-4088.
[63]   王亚清, 陶婷婷, 秦建华. 类器官芯片. 中国科学(生命科学), 2023, 53(2): 211-220.
[63]   Wang Y Q, Tao T T, Qin J H. Organoids-on-a-chip. Scientia Sinica (Vitae), 2023, 53(2): 211-220.
[64]   Park S E, Georgescu A, Huh D. Organoids-on-a-chip. Science, 2019, 364(6444): 960-965.
doi: 10.1126/science.aaw7894 pmid: 31171693
[65]   Tao T T, Wang Y Q, Chen W W, et al. Engineering human islet organoids from iPSCs using an organ-on-chip platform. Lab on a Chip, 2019, 19(6): 948-958.
doi: 10.1039/c8lc01298a pmid: 30719525
[66]   Ronaldson-Bouchard K, Teles D, Yeager K, et al. A multi-organ chip with matured tissue niches linked by vascular flow. Nature Biomedical Engineering, 2022, 6(4): 351-371.
doi: 10.1038/s41551-022-00882-6 pmid: 35478225
[67]   Joshi R, Castro De Moura M, Piñeyro D, et al. The DNA methylation landscape of human cancer organoids available at the American type culture collection. Epigenetics, 2020, 15(11): 1167-1177.
doi: 10.1080/15592294.2020.1762398
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