类器官及其应用的研究进展
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摘要
类器官弥补了传统研究中细胞简单模型与动物复杂模型的不足,为生命体关键功能研究提供了重要实验基础,已成为当前研究热点,并在疾病机理研究、药物筛选、再生医学、生物材料评价等方面具有重大理论意义和应用前景.本文对近10年类器官研究进行了综述,阐述出类器官研究的发展历程和研究现状,重点综述了类器官的主要研究领域,并解析类器官研究中存在的关键科学问题,为类器官在生物医药、再生医学和疾病精准治疗领域的研究和应用提供新思路.
Organoid can make up for the deficiency of cell models and animal models commonly used in traditional research. And it also provides an important experimental basis for the study of key functional studies of living organisms. At the present stage, organoid model has become a hot research field and is of great significance in disease mechanism research, drug screening, regenerative medicine, and biomedical material evaluation. In this paper, the research of organoids in the past 10 years is reviewed. It summarizes the development history and research status of organoid research, and also focuses on the main research fields of organoids. In addition, this paper mainly analyzes the key scientific issues in the study of organoids and propose ideas for organoid in biomedicine, regenerative medicine and precise treatment of diseases.
Organoid can make up for the deficiency of cell models and animal models commonly used in traditional research. And it also provides an important experimental basis for the study of key functional studies of living organisms. At the present stage, organoid model has become a hot research field and is of great significance in disease mechanism research, drug screening, regenerative medicine, and biomedical material evaluation. In this paper, the research of organoids in the past 10 years is reviewed. It summarizes the development history and research status of organoid research, and also focuses on the main research fields of organoids. In addition, this paper mainly analyzes the key scientific issues in the study of organoids and propose ideas for organoid in biomedicine, regenerative medicine and precise treatment of diseases.
引文
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[13] Lancaster M A, Magdalena R, Carol-Anne M, et al. Cerebral organoids model human brain development and microcephaly.Movement Disorders, 2013, 501(7467):373-378
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[15] Au S H, Chamberlain M D, Mahesh S, et al. Hepatic organoids for microfluidic drug screening. Lab on A Chip, 2014, 14(17):3290-3299
[16] Leite S B, Roosens T, Taghdouini A E, et al. Novel human hepatic organoid model enables testing of drug-induced liver fibrosis in vitro. Biomaterials, 2016, 78:1-10
[17] Huch M, Dorrell C, Boj S F, et al. In vitro expansion of single Lgr5+liver stem cells induced by Wnt-driven regeneration.Nature, 2013, 494(7436):247-250
[18] Huch M, Bonfanti P, Boj S F, et al. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. Embo Journal, 2013, 32(20):2708-2721
[19] Morizane R, Lam A Q, Freedman B S, et al. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nature Biotechnology, 2015, 33(11):1193-1200
[20] Minoru T, Pei X, Er, Han S, Chiu, et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature, 2016, 526(7574):564-568
[21] Soragni A, Janzen D M, Johnson L M, et al. A designed inhibitor of p53 aggregation rescues p53 tumor-suppression in ovarian carcinomas. Cancer Cell, 2016, 29(1):90-103
[22] Mirjana K, Karen H, Volker B, et al. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nature Communications, 2015, 6:8989-8998
[23] Trisno S L, Philo K E, Mccracken K W, et al. Esophageal organoids from human pluripotent stem cells delineate Sox2functions during esophageal specification. Cell Stem Cell, 2018,23(4):501-515
[24] Nugraha B, Buono M F, Von Boehmer L, et al. Human cardiac organoids for disease modeling. Clinical Pharmacology&Therapeutics, 2018, 105(1):79-85
[25] Nantasanti, Sathidpak, Spee, et al. Disease modeling and gene therapy of copper storage disease in canine hepatic organoids.Stem Cell Reports, 2015, 5(5):895-907
[26] Kim G A, Spence J R, Takayama S. Bioengineering for intestinal organoid cultures. Current Opinion in Biotechnology, 2017,47:51-58
[27] Rheinwald J G, Green H. Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma. Cell, 1975,6(3):317-330
[28] Rheinwald J G, Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature,1977, 265(5593):421-424
[29] Spence J R, Mayhew C N, Rankin S A, et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature, 2011, 470(7332):105-109
[30] Lu W, Rettenmeier E, Paszek M, et al. Crypt organoids culture as an in vitro model in drug metabolism and cytotoxicity studies.Drug Metabolism&Disposition the Biological Fate of Chemicals,2017, 45(7):748-754
[31] Liu C, Oikonomopoulos A, Sayed N, et al. Modeling human diseases with induced pluripotent stem cells:from 2D to 3D and beyond. Development, 2018, 145(5):156166-156171
[32] Broutier L, Anderssonrolf A, Hindley C J, et al. Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nature Protocols, 2016, 11(9):1724-1743
[33] Choi J, Iich E, Lee J H. Organogenesis of adult lung in a dish:differentiation, disease and therapy. Developmental Biology,2016, 420(2):278-286
[34] Sachs N, De J L, Kopper O, et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell, 2018, 172(1-2):373-386
[35] Morizane R, Bonventre J V. Generation of nephron progenitor cells and kidney organoids from human pluripotent stem cells.Nature Protocols, 2016, 12(1):195-207
[36] Fiore D, Ramesh P, Proto M C, et al. Rimonabant kills colon cancer stem cells without inducing toxicity in normal colon organoids.Frontiers in Pharmacology, 2017, 8:949-950
[37] Bruens L, Snippert H J G. Expanding the tissue toolbox:deriving colon tissue from human pluripotent stem cells. Cell Stem Cell,2017, 21(1):3-5
[38] Pham M T, Pollock K M, Rose M D, et al. Generation of human vascularized brain organoids. Neuroreport, 2018, 29(7):588-593
[39] Walsh A J, Cook R S, Sanders M E, et al. Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Cancer Research, 2014, 74(18):5184-5194
[40] Simian M, Bissell M J. Organoids:A historical perspective of thinking in three dimensions. Journal of Cell Biology, 2017,216(1):31-40
[41] Miller A J, Dye B R, Ferrer-Torres D, et al. Generation of lung organoids from human pluripotent stem cells in vitro. Nature Protocols, 2019, 14:518-540
[42] Cheung K J, Edward G, Zena W, et al. Collective invasion in breast cancer requires a conserved basal epithelial program. Cell, 2013,155(7):1639-1651
[43] Dong G, Ian V, Andrea S, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell, 2014, 159(1):176-187
[44] Karthaus W, Iaquinta P, Drost J, et al. Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell,2014, 159(1):163-175
[45] Mills R J, Titmarsh D M, Koenig X, et al. Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. Proc Natl Acad Sci USA, 2017,114(40):e8372-e8381
[46] Kai W, Siu Tsan Y, Jiangchun X, et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nature Genetics, 2014, 46(6):573-582
[47] Van D W M, Francies H E, Francis J M, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell, 2015, 161(4):933-945
[48] Hirt M N, Hansen A, Eschenhagen T. Cardiac tissue engineering state of the art. Circulation Research, 2014, 114(2):354-367
[49] 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
[50] Sasaki N, Sachs N, Wiebrands K, et al. Reg4+deep crypt secretory cells function as epithelial niche for Lgr5+stem cells in colon.Proc NatlAcad Sci USA, 2016, 113(37):e5399-e5407
[51] Müeller B J, Zhdanov A V, Borisov S M, et al. Nanoparticle-based fluoroionophore for analysis of potassium ion dynamics in 3D tissue models and in vivo. Advanced Functional Materials, 2018,28(9). pii:1704598
[52] Siegel R L, Miller K D, Jemal A J. Cancer statistics, 2019. CA:A Cancer Journal for Clinicians, 2019, 69(1):7-34
[53] Zhao Y, Kankala R K, Wang S B, et al. Multi-organs-on-chips:towards long-term biomedical Investigations. Molecules, 2019,24(4):675-696
[54] Bhatia S N, Ingber D E. Microfluidic organs-on-chips. Nature Biotechnology, 2014, 32(8):760-772
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