Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine

Qigu Yao , Sheng Cheng , Qiaoling Pan , Jiong Yu , Guoqiang Cao , Lanjuan Li , Hongcui Cao

MedComm ›› 2024, Vol. 5 ›› Issue (10) : e735

PDF
MedComm ›› 2024, Vol. 5 ›› Issue (10) : e735 DOI: 10.1002/mco2.735
REVIEW

Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine

Author information +
History +
PDF

Abstract

Organoids are miniature, highly accurate representations of organs that capture the structure and unique functions of specific organs. Although the field of organoids has experienced exponential growth, driven by advances in artificial intelligence, gene editing, and bioinstrumentation, a comprehensive and accurate overview of organoid applications remains necessary. This review offers a detailed exploration of the historical origins and characteristics of various organoid types, their applications—including disease modeling, drug toxicity and efficacy assessments, precision medicine, and regenerative medicine—as well as the current challenges and future directions of organoid research. Organoids have proven instrumental in elucidating genetic cell fate in hereditary diseases, infectious diseases, metabolic disorders, and malignancies, as well as in the study of processes such as embryonic development, molecular mechanisms, and host–microbe interactions. Furthermore, the integration of organoid technology with artificial intelligence and microfluidics has significantly advanced large-scale, rapid, and cost-effective drug toxicity and efficacy assessments, thereby propelling progress in precision medicine. Finally, with the advent of high-performance materials, three-dimensional printing technology, and gene editing, organoids are also gaining prominence in the field of regenerative medicine. Our insights and predictions aim to provide valuable guidance to current researchers and to support the continued advancement of this rapidly developing field.

Keywords

animal models / disease model / drug screening organoids / personalized medicine

Cite this article

Download citation ▾
Qigu Yao, Sheng Cheng, Qiaoling Pan, Jiong Yu, Guoqiang Cao, Lanjuan Li, Hongcui Cao. Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine. MedComm, 2024, 5(10): e735 DOI:10.1002/mco2.735

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391): 1145-1147.

[2]

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4): 663-676.

[3]

Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009; 459(7244): 262-265.

[4]

Yi SA, Zhang Y, Rathnam C, Pongkulapa T, Lee KB. Bioengineering approaches for the advanced organoid research. Adv Mater. 2021; 33(45): e2007949.

[5]

Park DS, Kozaki T, Tiwari SK, et al. iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer. Nature. 2023; 623(7986): 397-405.

[6]

Hirami Y, Mandai M, Sugita S, et al. Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa. Cell Stem Cell. 2023; 30(12): 1585-1596.e6.

[7]

Sprangers J, Zaalberg IC, Maurice MM. Organoid-based modeling of intestinal development, regeneration, and repair. Cell Death Differ. 2021; 28(1): 95-107.

[8]

Zeng Y, Jin RU. Molecular pathogenesis, targeted therapies, and future perspectives for gastric cancer. Semin Cancer Biol. 2022; 86(3): 566-582. Pt.

[9]

Tran T, Song CJ, 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.

[10]

Song H, Weinstein HNW, Allegakoen P, et al. Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states. Nat Commun. 2022; 13(1): 141.

[11]

Rossi G, Manfrin A, Lutolf MP. Progress and potential in organoid research. Nat Rev Genet. 2018; 19(11): 671-687.

[12]

Kong J, Lee H, Kim D, et al. Network-based machine learning in colorectal and bladder organoid models predicts anti-cancer drug efficacy in patients. Nat Commun. 2020; 11(1): 5485.

[13]

Bai L, Wu Y, Li G, Zhang W, Zhang H, Su J. AI-enabled organoids: construction, analysis, and application. Bioact Mater. 2024; 31: 525-548.

[14]

Bentwich I. Pharma’s bio-AI revolution. Drug Discov Today. 2023; 28(5): 103515.

[15]

Shinozawa T, Kimura M, Cai Y, et al. High-fidelity drug-induced liver injury screen using human pluripotent stem cell-derived organoids. Gastroenterology. 2021; 160(3): 831-846.e10.

[16]

Deng S, Li C, Cao J, et al. Organ-on-a-chip meets artificial intelligence in drug evaluation. Theranostics. 2023; 13(13): 4526-4558.

[17]

Jgamadze D, Lim JT, Zhang Z, et al. Structural and functional integration of human forebrain organoids with the injured adult rat visual system. Cell Stem Cell. 2023; 30(2): 137-152.e7.

[18]

Sampaziotis F, Muraro D, Tysoe OC, et al. Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science. 2021; 371(6531): 839-846.

[19]

Watanabe S, Kobayashi S, Ogasawara N, et al. Transplantation of intestinal organoids into a mouse model of colitis. Nat Protoc. 2022; 17(3): 649-671.

[20]

Wilson HV. A new method by which sponges may be artificially reared. Science. 1907; 25(649): 912-915.

[21]

Prostate cancer organoids make debut. Cancer Discov. 2014; 4(11): 1248.

[22]

Takasato M, Er PX, Chiu HS, et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature. 2015; 526(7574): 564-568.

[23]

Lancaster MA, Knoblich JA. Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc. 2014; 9(10): 2329-2340.

[24]

Lancaster MA, Renner M, Martin CA, et al. Cerebral organoids model human brain development and microcephaly. Nature. 2013; 501(7467): 373-379.

[25]

Wimmer RA, Leopoldi A, Aichinger M, et al. Human blood vessel organoids as a model of diabetic vasculopathy. Nature. 2019; 565(7740): 505-510.

[26]

Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014; 345(6194): 1247125.

[27]

Yin X, Mead BE, Safaee H, Langer R, Karp JM, Levy O. Engineering stem cell organoids. Cell Stem Cell. 2016; 18(1): 25-38.

[28]

Kim J, Koo BK, Knoblich JA. Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol. 2020; 21(10): 571-584.

[29]

Garreta E, Kamm RD, Chuva de Sousa Lopes SM, et al. Rethinking organoid technology through bioengineering. Nat Mater. 2021; 20(2): 145-155.

[30]

Vanslambrouck JM, Tan KS, Mah S, Little MH. Generation of proximal tubule-enhanced kidney organoids from human pluripotent stem cells. Nat Protoc. 2023; 18(11): 3229-3252.

[31]

Drakhlis L, Biswanath S, Farr CM, et al. Human heart-forming organoids recapitulate early heart and foregut development. Nat Biotechnol. 2021; 39(6): 737-746.

[32]

Cowan CS, Renner M, De Gennaro M, et al. Cell types of the human retina and its organoids at single-cell resolution. Cell. 2020; 182(6): 1623-1640.e34.

[33]

Pleguezuelos-Manzano C, Puschhof J, van den Brink S, Geurts V, Beumer J, Clevers H. Establishment and culture of human intestinal organoids derived from adult stem cells. Curr Protoc Immunol. 2020; 130(1): e106.

[34]

Prior N, Inacio P, Huch M. Liver organoids: from basic research to therapeutic applications. Gut. 2019; 68(12): 2228-2237.

[35]

Boj SF, Hwang CI, Baker LA, et al. Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015; 160(1-2): 324-338.

[36]

Xu H, Jiao D, Liu A, Wu K. Tumor organoids: applications in cancer modeling and potentials in precision medicine. J Hematol Oncol. 2022; 15(1): 58.

[37]

Bullmore E, Sporns O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci. 2009; 10(3): 186-198.

[38]

Qian X, Song H, Ming GL. Brain organoids: advances, applications and challenges. Development. 2019; 146(8): dev166074.

[39]

Mansour AA, Gonçalves JT, Bloyd CW, et al. An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol. 2018; 36(5): 432-441.

[40]

Pellegrini L, Bonfio C, Chadwick J, Begum F, Skehel M, Lancaster MA. Human CNS barrier-forming organoids with cerebrospinal fluid production. Science. 2020; 369(6500): eaaz5626.

[41]

Schafer ST, Mansour AA, Schlachetzki JCM, et al. An in vivo neuroimmune organoid model to study human microglia phenotypes. Cell. 2023; 186(10): 2111-2126.e20.

[42]

Garcez PP, Loiola EC, Madeiro da Costa R, et al. Zika virus impairs growth in human neurospheres and brain organoids. Science. 2016; 352(6287): 816-818.

[43]

Martínez-Mármol R, Giordano-Santini R, Kaulich E, et al. SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity. Sci Adv. 2023; 9(23): eadg2248.

[44]

Mesci P, de Souza JS, Martin-Sancho L, et al. SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir. PLoS Biol. 2022; 20(11): e3001845.

[45]

Velasco S, Kedaigle AJ, Simmons SK, et al. Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature. 2019; 570(7762): 523-527.

[46]

Chen X, Sun G, Tian E, et al. Modeling sporadic Alzheimer’s disease in human brain organoids under serum exposure. Adv Sci. 2021; 8(18): e2101462.

[47]

Lavazza A, Massimini M. Cerebral organoids: ethical issues and consciousness assessment. J Med Ethics. 2018; 44(9): 606-610.

[48]

Jeziorski J, Brandt R, Evans JH, et al. Brain organoids, consciousness, ethics and moral status. Semin Cell Dev Biol. 2023; 144: 97-102.

[49]

Trujillo CA, Gao R, Negraes PD, et al. Complex oscillatory waves emerging from cortical organoids model early human brain network development. Cell Stem Cell. 2019; 25(4): 558-569.e7.

[50]

Camp JG, Badsha F, Florio M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci USA. 2015; 112(51): 15672-15677.

[51]

O’Hara-Wright M, Gonzalez-Cordero A. Retinal organoids: a window into human retinal development. Development. 2020; 147(24): dev189746.

[52]

Eiraku M, Takata N, Ishibashi H, et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature. 2011; 472(7341): 51-56.

[53]

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.

[54]

Zhong X, Gutierrez C, Xue T, et al. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nat Commun. 2014; 5: 4047.

[55]

Achberger K, Probst C, Haderspeck J, et al. Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform. eLife. 2019; 8.

[56]

Burgoyne T, Lane A, Laughlin WE, Cheetham ME, Futter CE. Correlative light and immuno-electron microscopy of retinal tissue cryostat sections. PLoS One. 2018; 13(1): e0191048.

[57]

da Silva S, Cepko CL. Fgf8 expression and degradation of retinoic acid are required for patterning a high-acuity area in the retina. Dev Cell. 2017; 42(1): 68-81.e6.

[58]

DiStefano T, Chen HY, Panebianco C, et al. Accelerated and improved differentiation of retinal organoids from pluripotent stem cells in rotating-wall vessel bioreactors. Stem Cell Rep. 2018; 10(1): 300-313.

[59]

Zeng Z, Huang B, Parvez RK, et al. Generation of patterned kidney organoids that recapitulate the adult kidney collecting duct system from expandable ureteric bud progenitors. Nat Commun. 2021; 12(1): 3641.

[60]

Taguchi A, Kaku Y, Ohmori T, et al. Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell. 2014; 14(1): 53-67.

[61]

Takasato M, Er PX, Becroft M, et al. Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat Cell Biol. 2014; 16(1): 118-126.

[62]

Combes AN, Zappia L, Er PX, Oshlack A, Little MH. Single-cell analysis reveals congruence between kidney organoids and human fetal kidney. Genome Med. 2019; 11(1): 3.

[63]

Trush O, Takasato M. Kidney organoid research: current status and applications. Curr Opin Genet Dev. 2022; 75: 101944.

[64]

Wu H, Uchimura K, Donnelly EL, Kirita Y, Morris SA, Humphreys BD. Comparative analysis and refinement of human PSC-derived kidney organoid differentiation with single-cell transcriptomics. Cell Stem Cell. 2018; 23(6): 869-881.e8.

[65]

Lawlor KT, Vanslambrouck JM, Higgins JW, et al. Cellular extrusion bioprinting improves kidney organoid reproducibility and conformation. Nat Mater. 2021; 20(2): 260-271.

[66]

Lee AS, Tang C, Rao MS, Weissman IL, Wu JC. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat Med. 2013; 19(8): 998-1004.

[67]

Stein MC, Braun F, Krebs CF, Bunders MJ. Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities. Cell Tissue Res. 2021; 385(2): 457-473.

[68]

Shi M, McCracken KW, Patel AB, et al. Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types. Nat Biotechnol. 2023; 41(2): 252-261.

[69]

Krebs CF, Panzer U. Plasticity and heterogeneity of Th17 in immune-mediated kidney diseases. J Autoimmun. 2018; 87: 61-68.

[70]

Zea AH, Stewart T, Ascani J, et al. Activation of the IL-2 receptor in podocytes: a potential mechanism for podocyte injury in idiopathic nephrotic syndrome? PLoS One. 2016; 11(7): e0157907.

[71]

Rossi G, Broguiere N, Miyamoto M, et al. Capturing cardiogenesis in gastruloids. Cell Stem Cell. 2021; 28(2): 230-240.e6.

[72]

Kim H, Kamm RD, Vunjak-Novakovic G, Wu JC. Progress in multicellular human cardiac organoids for clinical applications. Cell Stem Cell. 2022; 29(4): 503-514.

[73]

Giacomelli E, Bellin M, Sala L, et al. Three-dimensional cardiac microtissues composed of cardiomyocytes and endothelial cells co-differentiated from human pluripotent stem cells. Development. 2017; 144(6): 1008-1017.

[74]

Hofbauer P, Jahnel SM, Papai N, et al. Cardioids reveal self-organizing principles of human cardiogenesis. Cell. 2021; 184(12): 3299-3317.e22.

[75]

Lewis-Israeli YR, Wasserman AH, Gabalski MA, et al. Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat Commun. 2021; 12(1): 5142.

[76]

Varzideh F, Pahlavan S, Ansari H, et al. Human cardiomyocytes undergo enhanced maturation in embryonic stem cell-derived organoid transplants. Biomaterials. 2019; 192: 537-550.

[77]

Lee SG, Kim YJ, Son MY, et al. Generation of human iPSCs derived heart organoids structurally and functionally similar to heart. Biomaterials. 2022; 290: 121860.

[78]

Suryawanshi H, Clancy R, Morozov P, Halushka MK, Buyon JP, Tuschl T. Cell atlas of the foetal human heart and implications for autoimmune-mediated congenital heart block. Cardiovasc Res. 2020; 116(8): 1446-1457.

[79]

Alysandratos KD, Herriges MJ, Kotton DN. Epithelial stem and progenitor cells in lung repair and regeneration. Annu Rev Physiol. 2021; 83: 529-550.

[80]

Barkauskas CE, Cronce MJ, Rackley CR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest. 2013; 123(7): 3025-3036.

[81]

Longmire TA, Ikonomou L, Hawkins F, et al. Efficient derivation of purified lung and thyroid progenitors from embryonic stem cells. Cell Stem Cell. 2012; 10(4): 398-411.

[82]

Mou H, Vinarsky V, Tata PR, et al. Dual SMAD signaling inhibition enables long-term expansion of diverse epithelial basal cells. Cell Stem Cell. 2016; 19(2): 217-231.

[83]

Sachs N, Papaspyropoulos A, Zomer-van Ommen DD, et al. Long-term expanding human airway organoids for disease modeling. EMBO J. 2019; 38(4): e100300.

[84]

Wang J, Li X, Chen H. Organoid models in lung regeneration and cancer. Cancer Lett. 2020; 475: 129-135.

[85]

Shi R, Radulovich N, Ng C, et al. Organoid cultures as preclinical models of non-small cell lung cancer. Clin Cancer Res. 2020; 26(5): 1162-1174.

[86]

Zhu J, Zhou J, Feng B, et al. MSCs alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of macrophages in mouse lung organoid-macrophage model. Cell Mol Life Sci. 2024; 81(1): 124.

[87]

Chen YW, Huang SX, de Carvalho A, et al. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biol. 2017; 19(5): 542-549.

[88]

Chiu MC, Li C, Liu X, et al. A bipotential organoid model of respiratory epithelium recapitulates high infectivity of SARS-CoV-2 Omicron variant. Cell Discov. 2022; 8(1): 57.

[89]

Sungnak W, Huang N, Bécavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020; 26(5): 681-687.

[90]

Katsura H, Sontake V, Tata A, et al. Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2-mediated interferon responses and pneumocyte dysfunction. Cell Stem Cell. 2020; 27(6): 890-904.e8.

[91]

Zhao S, Wu X, Tan Z, et al. Generation of human embryonic stem cell-derived lung organoids for modeling infection and replication differences between human adenovirus types 3 and 55 and evaluating potential antiviral drugs. J Virol. 2023; 97(5): e0020923.

[92]

Rijsbergen LC, Lamers MM, Comvalius AD, et al. Human respiratory syncytial virus subgroup A and B infections in nasal, bronchial, small-airway, and organoid-derived respiratory cultures. mSphere. 2021; 6(3): e00237-e00321.

[93]

Hui KPY, Ching RHH, Chan SKH, et al. Tropism, replication competence, and innate immune responses of influenza virus: an analysis of human airway organoids and ex-vivo bronchus cultures. Lancet Respir Med. 2018; 6(11): 846-854.

[94]

Chung MI, Bujnis M, Barkauskas CE, Kobayashi Y, Hogan BLM. Niche-mediated BMP/SMAD signaling regulates lung alveolar stem cell proliferation and differentiation. Development. 2018; 145(9).

[95]

Almazroo OA, Miah MK, Venkataramanan R. Drug metabolism in the liver. Clin Liver Dis. 2017; 21(1): 1-20.

[96]

Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol. 2017; 27(21): R1147-R1151.

[97]

Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013; 494(7436): 247-250.

[98]

Huch M, Gehart H, van Boxtel R, et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell. 2015; 160(1-2): 299-312.

[99]

Zhang Z, Wu Y, Xuan Z, Xu H, Yin S, Meng Z. Self-assembly of three-dimensional liver organoids: virtual reconstruction via endocytosed polymer dots for refactoring the fine structure. Biomater Sci. 2023; 11(24): 7867-7883.

[100]

Chen W, Lin F, Feng X, et al. MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation. Asian J Pharm Sci. 2024; 19(1): 100889.

[101]

Hendriks D, Artegiani B, Hu H, Chuva de Sousa Lopes S, Clevers H. Establishment of human fetal hepatocyte organoids and CRISPR-Cas9-based gene knockin and knockout in organoid cultures from human liver. Nat Protoc. 2021; 16(1): 182-217.

[102]

Guan Y, Enejder A, Wang M, et al. A human multi-lineage hepatic organoid model for liver fibrosis. Nat Commun. 2021; 12(1): 6138.

[103]

Dmitrieva-Posocco O, Wong AC, Lundgren P, et al. β-Hydroxybutyrate suppresses colorectal cancer. Nature. 2022; 605(7908): 160-165.

[104]

Saorin G, Caligiuri I, Rizzolio F. Microfluidic organoids-on-a-chip: the future of human models. Semin Cell Dev Biol. 2023; 144: 41-54.

[105]

Qu M, Xiong L, Lyu Y, et al. Establishment of intestinal organoid cultures modeling injury-associated epithelial regeneration. Cell Res. 2021; 31(3): 259-271.

[106]

Lindemans CA, Calafiore M, Mertelsmann AM, et al. Interleukin-22 promotes intestinal-stem-cell-mediated epithelial regeneration. Nature. 2015; 528(7583): 560-564.

[107]

Fujii M, Shimokawa M, Date S, et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell. 2016; 18(6): 827-838.

[108]

Kolawole AO, Mirabelli C, Hill DR, et al. Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape. PLoS Pathog. 2019; 15(10): e1008057.

[109]

Forbester JL, Goulding D, Vallier L, et al. Interaction of Salmonella enterica Serovar Typhimurium with intestinal organoids derived from human induced pluripotent stem cells. Infect Immun. 2015; 83(7): 2926-2934.

[110]

Nickerson KP, Llanos-Chea A, Ingano L, et al. A versatile human intestinal organoid-derived epithelial monolayer model for the study of enteric pathogens. Microbiol Spectr. 2021; 9(1): e0000321.

[111]

Dutta D, Heo I, O’Connor R. Studying cryptosporidium infection in 3D tissue-derived human organoid culture systems by microinjection. J Vis Exp. 2019;(151).

[112]

Brevini T, Maes M, Webb GJ, et al. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature. 2023; 615(7950): 134-142.

[113]

Bozzetti V, Senger S. Organoid technologies for the study of intestinal microbiota-host interactions. Trends Mol Med. 2022; 28(4): 290-303.

[114]

Puschhof J, Pleguezuelos-Manzano C, Martinez-Silgado A, et al. Intestinal organoid cocultures with microbes. Nat Protoc. 2021; 16(10): 4633-4649.

[115]

Bein A, Shin W, Jalili-Firoozinezhad S, et al. Microfluidic organ-on-a-chip models of human intestine. Cell Mol Gastroenterol Hepatol. 2018; 5(4): 659-668.

[116]

Hansen SL, Larsen HL, Pikkupeura LM, et al. An organoid-based CRISPR-Cas9 screen for regulators of intestinal epithelial maturation and cell fate. Sci Adv. 2023; 9(28): eadg4055.

[117]

Lo YH, Kolahi KS, Du Y, et al. A CRISPR/Cas9-engineered ARID1A-deficient human gastric cancer organoid model reveals essential and nonessential modes of oncogenic transformation. Cancer Discov. 2021; 11(6): 1562-1581.

[118]

Michels BE, Mosa MH, Streibl BI, et al. Pooled in vitro and in vivo CRISPR-Cas9 screening identifies tumor suppressors in human colon organoids. Cell Stem Cell. 2020; 26(5): 782-792.e7.

[119]

Giandomenico SL, Mierau SB, Gibbons GM, et al. Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output. Nat Neurosci. 2019; 22(4): 669-679.

[120]

Tian J, Yang J, Chen T, et al. Generation of human endometrial assembloids with a luminal epithelium using air-liquid interface culture methods. Adv Sci. 2023; 10(30): e2301868.

[121]

Pleguezuelos-Manzano C, Puschhof J, Rosendahl Huber A, et al. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli. Nature. 2020; 580(7802): 269-273.

[122]

Aisenbrey EA, Murphy WL. Synthetic alternatives to Matrigel. Nat Rev Mater. 2020; 5(7): 539-551.

[123]

Rizwan M, Ling C, Guo C, et al. Viscoelastic Notch signaling hydrogel induces liver bile duct organoid growth and morphogenesis. Adv Healthc Mater. 2022; 11(23): e2200880.

[124]

Nikolaev M, Mitrofanova O, Broguiere N, et al. Homeostatic mini-intestines through scaffold-guided organoid morphogenesis. Nature. 2020; 585(7826): 574-578.

[125]

Ritzau-Reid KI, Callens SJP, Xie R, et al. Microfibrous scaffolds guide stem cell lumenogenesis and brain organoid engineering. Adv Mater. 2023; 35(41): e2300305.

[126]

Ramli MNB, Lim YS, Koe CT, et al. Human pluripotent stem cell-derived organoids as models of liver disease. Gastroenterology. 2020; 159(4): 1471-1486.e12.

[127]

Parmentier T, LaMarre J, Lalonde J. Evaluation of neurotoxicity with human pluripotent stem cell-derived cerebral organoids. Curr Protoc. 2023; 3(4): e744.

[128]

Quintard C, Tubbs E, Jonsson G, et al. A microfluidic platform integrating functional vascularized organoids-on-chip. Nat Commun. 2024; 15(1): 1452.

[129]

Abdulla A, Chen S, Chen Z, et al. Three-dimensional microfluidics with dynamic fluidic perturbation promotes viability and uniformity of human cerebral organoids. Biosens Bioelectron. 2023; 240: 115635.

[130]

Renner H, Schöler HR, Bruder JM. Combining automated organoid workflows with artificial intelligence-based analyses: opportunities to build a new generation of interdisciplinary high-throughput screens for Parkinson’s disease and beyond. Mov Disord. 2021; 36(12): 2745-2762.

[131]

Singaraju JP, Kadiresan A, Bhoi RK, Gomez AH, Ma Z, Yang H. Organalysis: multifunctional image preprocessing and analysis software for cardiac organoid studies. Tissue Eng Part C, Methods. 2023; 29(12): 572-582.

[132]

Schuth S, Le Blanc S, Krieger TG, et al. Patient-specific modeling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system. J Exp Clin Cancer Res. 2022; 41(1): 312.

[133]

Kakni P, Truckenmüller R, Habibović P, van Griensven M, Giselbrecht S. A microwell-based intestinal organoid-macrophage co-culture system to study intestinal inflammation. Int J Mol Sci. 2022; 23(23).

[134]

Lim JTC, Kwang LG, Ho NCW, et al. Hepatocellular carcinoma organoid co-cultures mimic angiocrine crosstalk to generate inflammatory tumor microenvironment. Biomaterials. 2022; 284: 121527.

[135]

Shukla P, Yeleswarapu S, Heinrich MA, Prakash J, Pati F. Mimicking tumor microenvironment by 3D bioprinting: 3D cancer modeling. Biofabrication. 2022; 14(3).

[136]

Nguyen VVT, Ye S, Gkouzioti V, et al. A human kidney and liver organoid-based multi-organ-on-a-chip model to study the therapeutic effects and biodistribution of mesenchymal stromal cell-derived extracellular vesicles. J Extracell Vesicles. 2022; 11(11): e12280.

[137]

Bachman NJ, Riggs PK, Siddiqui N, Makris GJ, Womack JE, Lomax MI. Structure of the human gene (COX6A2) for the heart/muscle isoform of cytochrome c oxidase subunit VIa and its chromosomal location in humans, mice, and cattle. Genomics. 1997; 42(1): 146-151.

[138]

Makowska A, Kontny U, Weiskirchen R. HeLa cells cross-contaminated nasopharyngeal carcinoma cell lines: still a common problem. Br J Cancer. 2024; 130(12): 1885-1886.

[139]

Shao T, Chen YL. Stop using the misidentified cell line—LO2 as a human hepatocyte. J Hepatol. 2023.

[140]

Cao F, Sun H, Yang Z, et al. Multiple approaches revealed MGc80-3 as a somatic hybrid with HeLa cells rather than a gastric cancer cell line. Int J Cancer. 2024; 154(1): 155-168.

[141]

Sato K, Zhang W, Safarikia S, et al. Organoids and spheroids as models for studying cholestatic liver injury and cholangiocarcinoma. Hepatology (Baltimore, Md). 2021; 74(1): 491-502.

[142]

Astashkina AI, Mann BK, Prestwich GD, Grainger DW. Comparing predictive drug nephrotoxicity biomarkers in kidney 3-D primary organoid culture and immortalized cell lines. Biomaterials. 2012; 33(18): 4712-4721.

[143]

Sachs N, de Ligt J, Kopper O, et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell. 2018; 172(1-2): 373-386.e10.

[144]

van Riet S, van Schadewijk A, Khedoe P, et al. Organoid-based expansion of patient-derived primary alveolar type 2 cells for establishment of alveolus epithelial lung-chip cultures. Am J Physiol Lung Cell Mol Physiol. 2022; 322(4): L526-L538.

[145]

Dutta D, Heo I, Clevers H. Disease modeling in stem cell-derived 3D organoid systems. Trends Mol Med. 2017; 23(5): 393-410.

[146]

Yoshimura Y, Muto Y, Ledru N, et al. A single-cell multiomic analysis of kidney organoid differentiation. Proc Natl Acad Sci USA. 2023; 120(20): e2219699120.

[147]

Tan SY, Feng X, Cheng LKW, Wu AR. Vascularized human brain organoid on-chip. Lab Chip. 2023; 23(12): 2693-2709.

[148]

!!! INVALID CITATION !!! {};

[149]

Hukriede NA, Soranno DE, Sander V, et al. Experimental models of acute kidney injury for translational research. Nat Rev Nephrol. 2022; 18(5): 277-293.

[150]

Shcheglovitov A, Peterson RT. Screening platforms for genetic epilepsies-zebrafish, iPSC-derived neurons, and organoids. Neurotherapeutics. 2021; 18(3): 1478-1489.

[151]

Yoon YJ, Kim D, Tak KY, et al. Salivary gland organoid culture maintains distinct glandular properties of murine and human major salivary glands. Nat Commun. 2022; 13(1): 3291.

[152]

Kim M, Mun H, Sung CO, et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat Commun. 2019; 10(1): 3991.

[153]

Haider S, Beristain AG. Human organoid systems in modeling reproductive tissue development, function, and disease. Hum Reprod. 2023; 38(8): 1449-1463.

[154]

Liang J, Liu Y. Animal models of kidney disease: challenges and perspectives. Kidney360. 2023; 4(10): 1479-1493.

[155]

Hoffmann P, Schnepel N, Langeheine M, et al. Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine. PLoS One. 2021; 16(8): e0256143.

[156]

Runft S, Färber I, Krüger J, et al. Alternatives to animal models and their application in the discovery of species susceptibility to SARS-CoV-2 and other respiratory infectious pathogens: a review. Vet Pathol. 2022; 59(4): 565-577.

[157]

Boby N, Cao X, Williams K, et al. Simian immunodeficiency virus infection mediated changes in jejunum and peripheral SARS-CoV-2 receptor ACE2 and associated proteins or genes in rhesus macaques. Front Immunol. 2022; 13: 835686.

[158]

Fair SR, Schwind W, Julian DL, et al. Cerebral organoids containing an AUTS2 missense variant model microcephaly. Brain. 2023; 146(1): 387-404.

[159]

Dao L, You Z, Lu L, et al. Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids. Cell Stem Cell. 2024; 31(6): 818-833.e11.

[160]

Wulansari N, Darsono WHW, Woo HJ, et al. Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson’s disease-linked DNAJC6 mutations. Sci Adv. 2021; 7(8): eabb1540.

[161]

Lin YT, Seo J, Gao F, et al. APOE4 causes widespread molecular and cellular alterations associated with Alzheimer’s disease phenotypes in human iPSC-derived brain cell types. Neuron. 2018; 98(6): 1141-1154.e7.

[162]

Zhao J, Fu Y, Yamazaki Y, et al. APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids. Nat Commun. 2020; 11(1): 5540.

[163]

Song E, Zhang C, Israelow B, et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021; 218(3): e20202135.

[164]

Jacob F, Salinas RD, Zhang DY, et al. A patient-derived glioblastoma organoid model and biobank recapitulates inter-and intra-tumoral heterogeneity. Cell. 2020; 180(1): 188-204.e22.

[165]

Norrie JL, Nityanandam A, Lai K, et al. Retinoblastoma from human stem cell-derived retinal organoids. Nat Commun. 2021; 12(1): 4535.

[166]

Kruczek K, Qu Z, Gentry J, et al. Gene therapy of dominant CRX-Leber congenital amaurosis using patient stem cell-derived retinal organoids. Stem Cell Rep. 2021; 16(2): 252-263.

[167]

Chiu MC, Li C, Liu X, et al. Human nasal organoids model SARS-CoV-2 upper respiratory infection and recapitulate the differential infectivity of emerging variants. mBio. 2022; 13(4): e0194422.

[168]

Xiao H, Liang J, Liu S, et al. Proteomics and organoid culture reveal the underlying pathogenesis of Hashimoto’s thyroiditis. Front Immunol. 2021; 12: 784975.

[169]

van der Vaart J, Bosmans L, Sijbesma SF, et al. Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism. Proc Natl Acad Sci USA. 2021; 118(51).

[170]

Chen D, Tan Y, Li Z, et al. Organoid cultures derived from patients with papillary thyroid cancer. J Clin Endocrinol Metab. 2021; 106(5): 1410-1426.

[171]

Richards DJ, Li Y, Kerr CM, et al. Human cardiac organoids for the modelling of myocardial infarction and drug cardiotoxicity. Nat Biomed Eng. 2020; 4(4): 446-462.

[172]

Leoni Swart A, Laventie BJ, Sütterlin R, et al. Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model. Nat Microbiol. 2024; 9(7): 1725-1737.

[173]

Salahudeen AA, Choi SS, Rustagi A, et al. Progenitor identification and SARS-CoV-2 infection in human distal lung organoids. Nature. 2020; 588(7839): 670-675.

[174]

Soroka CJ, Assis DN, Alrabadi LS, et al. Bile-derived organoids from patients with primary sclerosing cholangitis recapitulate their inflammatory immune profile. Hepatology. 2019; 70(3): 871-882.

[175]

Amarachintha SP, Mourya R, Ayabe H, et al. Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia. Hepatology. 2022; 75(1): 89-103.

[176]

Broutier L, Mastrogiovanni G, Verstegen MM, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 2017; 23(12): 1424-1435.

[177]

Meyers NL, Ashuach T, Lyons DE, et al. Hepatitis C virus infects and perturbs liver stem cells. mBio. 2023:e0131823.

[178]

Li P, Li Y, Wang Y, et al. Recapitulating hepatitis E virus-host interactions and facilitating antiviral drug discovery in human liver-derived organoids. Sci Adv. 2022; 8(3): eabj5908.

[179]

De Crignis E, Hossain T, Romal S, et al. Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma. eLife. 2021; 10: e60747.

[180]

Liu B, Bukhari I, Li F, et al. Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating β-Catenin nuclear translocation. J Adv Res. 2024.

[181]

McCracken KW, Catá EM, Crawford CM, et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature. 2014; 516(7531): 400-404.

[182]

Zu M, Hao X, Ning J, et al. Patient-derived organoid culture of gastric cancer for disease modeling and drug sensitivity testing. Biomed Pharmacother. 2023; 163: 114751.

[183]

Kawasaki K, Toshimitsu K, Matano M, et al. An organoid biobank of neuroendocrine neoplasms enables genotype-phenotype mapping. Cell. 2020; 183(5): 1420-1435.e21.

[184]

van de Wetering M, Francies HE, Francis JM, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 2015; 161(4): 933-945.

[185]

Lamers MM, Beumer J, van der Vaart J, et al. SARS-CoV-2 productively infects human gut enterocytes. Science. 2020; 369(6499): 50-54.

[186]

Boilève A, Cartry J, Goudarzi N, et al. Organoids for functional precision medicine in advanced pancreatic cancer. Gastroenterology. 2024.

[187]

Breunig M, Merkle J, Wagner M, et al. Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells. Cell Stem Cell. 2021; 28(6): 1105-1124.e19.

[188]

Gupta N, Matsumoto T, Hiratsuka K, et al. Modeling injury and repair in kidney organoids reveals that homologous recombination governs tubular intrinsic repair. Sci Transl Med. 2022; 14(634): eabj4772.

[189]

Jansen J, Reimer KC, Nagai JS, et al. SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids. Cell Stem Cell. 2022; 29(2): 217-231.e8.

[190]

Liu M, Zhang C, Gong X, et al. Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo. Cell Stem Cell. 2024; 31(1): 52-70.e8.

[191]

Tse RT, Wong CY, Ding X, et al. The establishment of kidney cancer organoid line in drug testing. Cancer Med. 2024; 13(12): e7432.

[192]

Khan AO, Rodriguez-Romera A, Reyat JS, et al. Human bone marrow organoids for disease modeling, discovery, and validation of therapeutic targets in hematologic malignancies. Cancer Discov. 2023; 13(2): 364-385.

[193]

Lassche G, van Boxtel W, Aalders TW, et al. Development and characterization of patient-derived salivary gland cancer organoid cultures. Oral Oncol. 2022; 135: 106186.

[194]

Guillen KP, Fujita M, Butterfield AJ, et al. A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology. Nat Cancer. 2022; 3(2): 232-250.

[195]

Gao D, Vela I, Sboner A, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014; 159(1): 176-187.

[196]

Jung SY, You HJ, Kim MJ, Ko G, Lee S, Kang KS. Wnt-activating human skin organoid model of atopic dermatitis induced by Staphylococcus aureus and its protective effects by Cutibacterium acnes. iScience. 2022; 25(10): 105150.

[197]

Ou L, Liu S, Wang H, et al. Patient-derived melanoma organoid models facilitate the assessment of immunotherapies. EBioMed. 2023; 92: 104614.

[198]

Ma J, Liu J, Gao D, et al. Establishment of human pluripotent stem cell-derived skin organoids enabled pathophysiological model of SARS-CoV-2 infection. Adv Sci. 2022; 9(7): e2104192.

[199]

Choi EK, Rajendiran TM, Soni T, et al. The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease. Nat Commun. 2024; 15(1): 4775.

[200]

Hamed SA, Mohan A, Navaneetha Krishnan S, et al. Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3. Gut Microbes. 2023; 15(2): 2281011.

[201]

Li SR, Gulieva RE, Helms L, et al. Glucose absorption drives cystogenesis in a human organoid-on-chip model of polycystic kidney disease. Nat Commun. 2022; 13(1): 7918.

[202]

Becker S, L’Ecuyer Z, Jones BW, Zouache MA, McDonnell FS, Vinberg F. Modeling complex age-related eye disease. Prog Retin Eye Res. 2024:101247.

[203]

Chirco KR, Chew S, Moore AT, Duncan JL, Lamba DA. Allele-specific gene editing to rescue dominant CRX-associated LCA7 phenotypes in a retinal organoid model. Stem Cell Rep. 2021; 16(11): 2690-2702.

[204]

Huang KC, Wang ML, Chen SJ, et al. Morphological and molecular defects in human three-dimensional retinal organoid model of X-linked juvenile retinoschisis. Stem Cell Rep. 2019; 13(5): 906-923.

[205]

Dooves S, van Velthoven AJH, Suciati LG, Heine VM. Neuron-glia interactions in tuberous sclerosis complex affect the synaptic balance in 2D and organoid cultures. Cells. 2021; 10(1): 134.

[206]

Shaker MR, Slonchak A, Al-Mhanawi B, et al. Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2. Sci Adv. 2024; 10(23): eadj4735.

[207]

Werren EA, Peirent ER, Jantti H, et al. Biallelic variants in CSMD1 are implicated in a neurodevelopmental disorder with intellectual disability and variable cortical malformations. Cell Death Dis. 2024; 15(5): 379.

[208]

Heo I, Dutta D, Schaefer DA, et al. Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nat Microbiol. 2018; 3(7): 814-823.

[209]

van Dijk LLA, Rijsbergen LC, Rubio BT, et al. Virus neutralization assays for human respiratory syncytial virus using airway organoids. Cell Mol Life Sci. 2024; 81(1): 267.

[210]

Lamers MM, van der Vaart J, Knoops K, et al. An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells. EMBO J. 2021; 40(5): e105912.

[211]

Bartfeld S, Bayram T, van de Wetering M, et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology. 2015; 148(1): 126-136.e6.

[212]

Cao L, Zhu S, Lu H, et al. Helicobacter pylori-induced RASAL2 through activation of nuclear factor-κB promotes gastric tumorigenesis via β-catenin signaling axis. Gastroenterology. 2022; 162(6): 1716-1731.e17.

[213]

Ettayebi K, Crawford SE, Murakami K, et al. Replication of human noroviruses in stem cell-derived human enteroids. Science. 2016; 353(6306): 1387-1393.

[214]

Caiaffa CD, Tukeman G, Delgado CZ, et al. Dolutegravir induces FOLR1 expression during brain organoid development. Front Mol Neurosci. 2024; 17: 1394058.

[215]

Dos Reis RS, Selvam S, Wagner MCE, Ayyavoo V. Modeling HIV-1 infection in CNS via infected monocytes using immunocompetent brain organoids. Methods Mol Biol. 2024; 2807: 261-270.

[216]

Markus A, Lebenthal-Loinger I, Yang IH, Kinchington PR, Goldstein RS. An in vitro model of latency and reactivation of varicella zoster virus in human stem cell-derived neurons. PLoS Pathog. 2015; 11(6): e1004885.

[217]

Qian X, Nguyen HN, Song MM, et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell. 2016; 165(5): 1238-1254.

[218]

Krenn V, Bosone C, Burkard TR, et al. Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly. Cell Stem Cell. 2021; 28(8): 1362-1379.e7.

[219]

Zhang X, Lin H, Dong L, Xia Q. Recapitulating influenza virus infection and facilitating antiviral and neuroprotective screening in tractable brain organoids. Theranostics. 2022; 12(12): 5317-5329.

[220]

Taylor J, Sellin J, Kuerschner L, et al. Generation of immune cell containing adipose organoids for in vitro analysis of immune metabolism. Sci Rep. 2020; 10(1): 21104.

[221]

Escudero M, Vaysse L, Eke G, et al. Scalable generation of pre-vascularized and functional human beige adipose organoids. Adv Sci. 2023; 10(31): e2301499.

[222]

Wang S, Wang X, Tan Z, et al. Human ESC-derived expandable hepatic organoids enable therapeutic liver repopulation and pathophysiological modeling of alcoholic liver injury. Cell Res. 2019; 29(12): 1009-1026.

[223]

Kimura M, Iguchi T, Iwasawa K, et al. En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH. Cell. 2022; 185(22): 4216-4232.e16.

[224]

Ouchi R, Togo S, Kimura M, et al. Modeling steatohepatitis in humans with pluripotent stem cell-derived organoids. Cell Metab. 2019; 30(2): 374-384.e6..

[225]

Hendriks D, Brouwers JF, Hamer K, et al. Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis. Nat Biotechnol. 2023; 41(11): 1567-1581.

[226]

Lee SH, Hu W, Matulay JT, et al. Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell. 2018; 173(2): 515-528.e17.

[227]

Yan HHN, Siu HC, Law S, et al. A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening. Cell Stem Cell. 2018; 23(6): 882-897.e11.

[228]

Pasch CA, Favreau PF, Yueh AE, et al. Patient-derived cancer organoid cultures to predict sensitivity to chemotherapy and radiation. Clin Cancer Res. 2019; 25(17): 5376-5387.

[229]

Sun CP, Lan HR, Fang XL, Yang XY, Jin KT. Organoid models for precision cancer immunotherapy. Front Immunol. 2022; 13: 770465.

[230]

Kong JCH, Guerra GR, Millen RM, et al. Tumor-infiltrating lymphocyte function predicts response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. JCO Precis Oncol. 2018; 2: 1-15.

[231]

Cattaneo CM, Dijkstra KK, Fanchi LF, et al. Tumor organoid-T-cell coculture systems. Nat Protoc. 2020; 15(1): 15-39.

[232]

Dijkstra KK, Cattaneo CM, Weeber F, et al. Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids. Cell. 2018; 174(6): 1586-1598.e12.

[233]

Liu J, Li P, Wang L, et al. Cancer-associated fibroblasts provide a stromal niche for liver cancer organoids that confers trophic effects and therapy resistance. Cell Mol Gastroenterol Hepatol. 2021; 11(2): 407-431.

[234]

Atanasova VS, de Jesus Cardona C, Hejret V, et al. Mimicking tumor cell heterogeneity of colorectal cancer in a patient-derived organoid-fibroblast model. Cell Mol Gastroenterol Hepatol. 2023; 15(6): 1391-1419.

[235]

Xiang T, Wang J, Li H. Current applications of intestinal organoids: a review. Stem Cell Res Ther. 2024; 15(1): 155.

[236]

Lorenzo-Martín LF, Broguiere N, Langer J, et al. Patient-derived mini-colons enable long-term modeling of tumor-microenvironment complexity. Nat Biotechnol. 2024.

[237]

Mao Y, Wang W, Yang J, et al. Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids. Protein Cell. 2023.

[238]

Fatima I, Ahmad R, Barman S, et al. Albendazole inhibits colon cancer progression and therapy resistance by targeting ubiquitin ligase RNF20. Br J Cancer. 2024.

[239]

Sun L, Wan AH, Yan S, et al. A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance. Acta Pharm Sin B. 2024; 14(1): 223-240.

[240]

Shukla P, Bera AK, Ghosh A, Gaddam K, Pati F. Assessment and process optimization of high throughput biofabrication of immunocompetent breast cancer model for drug screening applications. Biofabrication. 2024.

[241]

Abady MM, Jeong JS, Kwon HJ, Assiri AM, Cho J, Saadeldin IM. The reprotoxic adverse side effects of neurogenic and neuroprotective drugs: current use of human organoid modeling as a potential alternative to preclinical models. Front Pharmacol. 2024; 15: 1412188.

[242]

Antón-Bolaños N, Faravelli I, Faits T, et al. Brain chimeroids reveal individual susceptibility to neurotoxic triggers. Nature. 2024; 631(8019): 142-149.

[243]

Ding B, Sun G, Liu S, et al. Three-dimensional renal organoids from whole kidney cells: generation, optimization, and potential application in nephrotoxicology in vitro. Cell Transplant. 2020; 29: 963689719897066.

[244]

Li D, Zhang R, Le Y, et al. Organoid-based assessment of metal-organic framework (MOF) nanomedicines for ex vivo cancer therapy. ACS Appl Mater Interfaces. 2024; 16(26): 33070-33080.

[245]

Qin X, Cao M, Peng T, et al. Features, potential invasion pathways, and reproductive health risks of microplastics detected in human uterus. Environ Sci Technol. 2024; 58(24): 10482-10493.

[246]

Kasendra M, Luc R, Yin J, et al. Duodenum Intestine-Chip for preclinical drug assessment in a human relevant model. eLife. 2020; 9.

[247]

Zhang K, Xi J, Wang Y, et al. A microfluidic chip-based automated system for whole-course monitoring the drug responses of organoids. Anal Chem. 2024; 96(24): 10092-10101.

[248]

Skardal A, Murphy SV, Devarasetty M, et al. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci Rep. 2017; 7(1): 8837.

[249]

Rajan SAP, Aleman J, Wan M, et al. Probing prodrug metabolism and reciprocal toxicity with an integrated and humanized multi-tissue organ-on-a-chip platform. Acta Biomater. 2020; 106: 124-135.

[250]

Maramraju S, Kowalczewski A, Kaza A, et al. AI-organoid integrated systems for biomedical studies and applications. Bioeng Transl Med. 2024; 9(2): e10641.

[251]

Matthews JM, Schuster B, Kashaf SS, et al. OrganoID: a versatile deep learning platform for tracking and analysis of single-organoid dynamics. PLoS Comput Biol. 2022; 18(11): e1010584.

[252]

Le Compte M, De La Hoz EC, Peeters S, et al. Single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer. NPJ Precis Oncol. 2023; 7(1): 128.

[253]

Carvalho MR, Truckenmuller R, Reis RL, Oliveira JM. Biomaterials and microfluidics for drug discovery and development. Adv Exp Med Biol. 2020; 1230: 121-135.

[254]

Balijepalli A, Sivaramakrishan V. Organs-on-chips: research and commercial perspectives. Drug Discov Today. 2017; 22(2): 397-403.

[255]

Busek M, Aizenshtadt A, Amirola-Martinez M, Delon L, Krauss S. Academic user view: organ-on-a-chip technology. Biosensors. 2022; 12(2).

[256]

Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018; 359(6378): 920-926.

[257]

Ji S, Feng L, Fu Z, et al. Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology. Sci Transl Med. 2023; 15(706): eadg3358.

[258]

Xian L, Zhao P, Chen X, et al. Heterogeneity, inherent and acquired drug resistance in patient-derived organoid models of primary liver cancer. Cell Oncol (Dordrecht). 2022; 45(5): 1019-1036.

[259]

Calandrini C, Schutgens F, Oka R, et al. An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity. Nat Commun. 2020; 11(1): 1310.

[260]

Mo S, Tang P, Luo W, et al. Patient-derived organoids from colorectal cancer with paired liver metastasis reveal tumor heterogeneity and predict response to chemotherapy. Adv Sci. 2022; 9(31): e2204097.

[261]

Mainardi S, Bernards R. A large-scale organoid-based screening platform to advance drug repurposing in pancreatic cancer. Cell Genomics. 2022; 2(2): 100100.

[262]

Senkowski W, Gall-Mas L, Falco MM, et al. A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids. Dev Cell. 2023; 58(12): 1106-1121.e7.

[263]

Lõhmussaar K, Oka R, Espejo Valle-Inclan J, et al. Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer. Cell Stem Cell. 2021; 28(8): 1380-1396.e6.

[264]

Mullenders J, de Jongh E, Brousali A, et al. Mouse and human urothelial cancer organoids: a tool for bladder cancer research. Proc Natl Acad Sci USA. 2019; 116(10): 4567-4574.

[265]

Yao Q, Chen W, Yu Y, et al. Human placental mesenchymal stem cells relieve primary sclerosing cholangitis via upregulation of TGR5 in Mdr2-/-mice and human intrahepatic cholangiocyte organoid models. Research (Washington, DC). 2023; 6: 0207.

[266]

Geurts MH, de Poel E, Amatngalim GD, et al. CRISPR-based adenine editors correct nonsense mutations in a cystic fibrosis organoid biobank. Cell Stem Cell. 2020; 26(4): 503-510.e7.

[267]

Yuan B, Zhao X, Wang X, et al. Patient-derived organoids for personalized gallbladder cancer modelling and drug screening. Clin Transl Med. 2022; 12(1): e678.

[268]

Phan N, Hong JJ, Tofig B, et al. A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids. Commun Biol. 2019; 2: 78.

[269]

Sykes M, Sachs DH. Progress in xenotransplantation: overcoming immune barriers. Nat Rev Nephrol. 2022; 18(12): 745-761.

[270]

Hsia GSP, Esposito J, da Rocha LA, Ramos SLG, Okamoto OK. Clinical application of human induced pluripotent stem cell-derived organoids as an alternative to organ transplantation. Stem Cells Int. 2021; 2021: 6632160.

[271]

Watson CL, Mahe MM, Múnera J, et al. An in vivo model of human small intestine using pluripotent stem cells. Nat Med. 2014; 20(11): 1310-1314.

[272]

Lakowski J, Welby E, Budinger D, et al. Isolation of human photoreceptor precursors via a cell surface marker panel from stem cell-derived retinal organoids and fetal retinae. Stem Cells. 2018; 36(5): 709-722.

[273]

Santos-Ferreira T, Völkner M, Borsch O, et al. Stem cell-derived photoreceptor transplants differentially integrate into mouse models of cone-rod dystrophy. Invest Ophthalmol Vis Sci. 2016; 57(7): 3509-3520.

[274]

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.

[275]

Willemse J, van Tienderen G, van Hengel E, et al. Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids. Biomaterials. 2022; 284: 121473.

[276]

Yoshihara E, O’Connor C, Gasser E, et al. Immune-evasive human islet-like organoids ameliorate diabetes. Nature. 2020; 586(7830): 606-611.

[277]

Weiner AI, Jackson SR, Zhao G, et al. Mesenchyme-free expansion and transplantation of adult alveolar progenitor cells: steps toward cell-based regenerative therapies. NPJ Regen Med. 2019; 4: 17.

[278]

Qian X, Jacob F, Song MM, Nguyen HN, Song H, Ming GL. Generation of human brain region-specific organoids using a miniaturized spinning bioreactor. Nat Protoc. 2018; 13(3): 565-580.

[279]

Song W, Lu YC, Frankel AS, An D, Schwartz RE, Ma M. Engraftment of human induced pluripotent stem cell-derived hepatocytes in immunocompetent mice via 3D co-aggregation and encapsulation. Sci Rep. 2015; 5: 16884.

[280]

Tang XY, Wu S, Wang D, et al. Human organoids in basic research and clinical applications. Signal Transduct Target Ther. 2022; 7(1): 168.

[281]

Licata JP, Schwab KH, Har-El YE, Gerstenhaber JA, Lelkes PI. Bioreactor technologies for enhanced organoid culture. Int J Mol Sci. 2023; 24(14).

[282]

Romero-Morales AI, O’Grady BJ, Balotin KM, Bellan LM, Lippmann ES, Gama V. Spin∞: an updated miniaturized spinning bioreactor design for the generation of human cerebral organoids from pluripotent stem cells. HardwareX. 2019; 6: 622-634.

[283]

Bouffi C, Wikenheiser-Brokamp KA, Chaturvedi P, et al. In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice. Nat Biotechnol. 2023; 41(6): 824-831.

[284]

Küçükköse E, Heesters BA, Villaudy J, et al. Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice. J Immunother Cancer. 2022; 10(12).

[285]

Ng XY, Peh GSL, Yam GH, Tay HG, Mehta JS. Corneal endothelial-like cells derived from induced pluripotent stem cells for cell therapy. Int J Mol Sci. 2023; 24(15).

[286]

Dong X, Xu SB, Chen X, et al. Human cerebral organoids establish subcortical projections in the mouse brain after transplantation. Mol Psychiatry. 2021; 26(7): 2964-2976.

[287]

Revah O, Gore F, Kelley KW, et al. Maturation and circuit integration of transplanted human cortical organoids. Nature. 2022; 610(7931): 319-326.

[288]

Zou T, Gao L, Zeng Y, et al. Organoid-derived C-Kit+/SSEA4-human retinal progenitor cells promote a protective retinal microenvironment during transplantation in rodents. Nat Commun. 2019; 10(1): 1205.

[289]

Lin B, McLelland BT, Aramant RB, et al. Retina organoid transplants develop photoreceptors and improve visual function in RCS rats with RPE dysfunction. Invest Ophthalmol Vis Sci. 2020; 61(11): 34.

[290]

Bannier-Hélaouët M, Post Y, Korving J, et al. Exploring the human lacrimal gland using organoids and single-cell sequencing. Cell Stem Cell. 2021; 28(7): 1221-1232.e7.

[291]

Hayashi R, Okubo T, Kudo Y, et al. Generation of 3D lacrimal gland organoids from human pluripotent stem cells. Nature. 2022; 605(7908): 126-131.

[292]

Ogundipe VML, Groen AH, Hosper N, et al. Generation and differentiation of adult tissue-derived human thyroid organoids. Stem Cell Rep. 2021; 16(4): 913-925.

[293]

Zeleniak A, Wiegand C, Liu W, et al. De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids. Nat Methods. 2022; 19(10): 1306-1319.

[294]

Dai X, Wang X, Yang C, et al. Human fibroblasts facilitate the generation of iPSCs-derived mammary-like organoids. Stem Cell Res Ther. 2022; 13(1): 377.

[295]

Tan Q, Choi KM, Sicard D, Tschumperlin DJ. Human airway organoid engineering as a step toward lung regeneration and disease modeling. Biomaterials. 2017; 113: 118-132.

[296]

Li L, Feng J, Zhao S, Rong Z, Lin Y. SOX9 inactivation affects the proliferation and differentiation of human lung organoids. Stem Cell Res Ther. 2021; 12(1): 343.

[297]

Takebe T, Sekine K, Kimura M, et al. Massive and reproducible production of liver buds entirely from human pluripotent stem cells. Cell Rep. 2017; 21(10): 2661-2670.

[298]

Zhang RR, Koido M, Tadokoro T, et al. Human iPSC-derived posterior gut progenitors are expandable and capable of forming gut and liver organoids. Stem Cell Rep. 2018; 10(3): 780-793.

[299]

Tsuchida T, Murata S, Hasegawa S, et al. Investigation of clinical safety of human iPS cell-derived liver organoid transplantation to infantile patients in porcine model. Cell Transplant. 2020; 29: 963689720964384.

[300]

Salas-Silva S, Kim Y, Kim TH, et al. Human chemically-derived hepatic progenitors (hCdHs) as a source of liver organoid generation: application in regenerative medicine, disease modeling, and toxicology testing. Biomaterials. 2023; 303: 122360.

[301]

Yuan X, Wu J, Sun Z, et al. Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure. Cell Stem Cell. 2024; 31(4): 484-498.

[302]

Sampaziotis F, Justin AW, Tysoe OC, et al. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nat Med. 2017; 23(8): 954-963.

[303]

Hohwieler M, Illing A, Hermann PC, et al. Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut. 2017; 66(3): 473-486.

[304]

van den Berg CW, Ritsma L, Avramut MC, et al. Renal subcapsular transplantation of PSC-derived kidney organoids induces neo-vasculogenesis and significant glomerular and tubular maturation in vivo. Stem Cell Rep. 2018; 10(3): 751-765.

[305]

Nam SA, Seo E, Kim JW, et al. Graft immaturity and safety concerns in transplanted human kidney organoids. Exp Mol Med. 2019; 51(11): 1-13.

[306]

Subramanian A, Sidhom EH, Emani M, et al. Single cell census of human kidney organoids shows reproducibility and diminished off-target cells after transplantation. Nat Commun. 2019; 10(1): 5462.

[307]

Kim JW, Nam SA, Yi J, et al. Kidney decellularized extracellular matrix enhanced the vascularization and maturation of human kidney organoids. Adv Sci. 2022; 9(15): e2103526.

[308]

Singh A, Poling HM, Chaturvedi P, et al. Transplanted human intestinal organoids: a resource for modeling human intestinal development. Development. 2023; 150(9): dev201416.

[309]

Múnera JO, Kechele DO, Bouffi C, et al. Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon. Cell Stem Cell. 2023; 30(11): 1434-1451.e9.

[310]

Hwang SY, Lee D, Lee G, et al. Endometrial organoids: a reservoir of functional mitochondria for uterine repair. Theranostics. 2024; 14(3): 954-972.

[311]

Ebner-Peking P, Krisch L, Wolf M, et al. Self-assembly of differentiated progenitor cells facilitates spheroid human skin organoid formation and planar skin regeneration. Theranostics. 2021; 11(17): 8430-8447.

[312]

Liu YC, Ansaryan S, Tan J, et al. Nanoplasmonic single-tumoroid microarray for real-time secretion analysis. Adv Sci. 2024:e2401539.

[313]

Ryu JR, Ko K, Sun W. Polarization of organoids by bioengineered symmetry breaking. IBRO Neurosci Rep. 2024; 17: 22-31.

[314]

Kim J, Kim J, Jin Y, Cho SW. In situbiosensing technologies for an organ-on-a-chip. Biofabrication. 2023; 15(4).

[315]

Li Z, Song P, Li G, et al. AI energized hydrogel design, optimization and application in biomedicine. Mater Today Bio. 2024; 25: 101014.

[316]

Kowalczewski A, Sun S, Mai NY, et al. Design optimization of geometrically confined cardiac organoids enabled by machine learning techniques. Cell Rep Methods. 2024; 4(6): 100798.

[317]

Lefferts JW, Kroes S, Smith MB, et al. OrgaSegment: deep-learning based organoid segmentation to quantify CFTR dependent fluid secretion. Commun Biol. 2024; 7(1): 319.

[318]

Shi H, Kowalczewski A, Vu D, et al. Organoid intelligence: integration of organoid technology and artificial intelligence in the new era of in vitro models. Med Novel Technol Devices. 2024; 21.

[319]

Kühl L, Graichen P, von Daacke N, et al. Human lung organoids—a novel experimental and precision medicine approach. Cells. 2023; 12(16).

[320]

Osonoi S, Takebe T. Organoid-guided precision hepatology for metabolic liver disease. J Hepatol. 2024; 80(5): 805-821.

[321]

Zhou C, Wu Y, Wang Z, et al. Standardization of organoid culture in cancer research. Cancer Med. 2023; 12(13): 14375-14386.

[322]

Gan Z, Qin X, Liu H, Liu J, Qin J. Recent advances in defined hydrogels in organoid research. Bioact Mater. 2023; 28: 386-401.

[323]

Sulaksono HLS, Annisa A, Ruslami R, et al. Recent advances in graphene oxide-based on organoid culture as disease model and cell behavior—a systematic literature review. Int J Nanomed. 2024; 19: 6201-6228.

[324]

Shrestha S, Lekkala VKR, Acharya P, Kang SY, Vanga MG, Lee MY. Reproducible generation of human liver organoids (HLOs) on a pillar plate platform via microarray 3D bioprinting. Lab Chip. 2024; 24(10): 2747-2761.

[325]

Lingard E, Dong S, Hoyle A, et al. Optimising a self-assembling peptide hydrogel as a Matrigel alternative for 3-dimensional mammary epithelial cell culture. Biomater Adv. 2024; 160: 213847.

[326]

Kataoka M, Gyngell C, Savulescu J, Sawai T. The importance of accurate representation of human brain organoid research. Trends Biotechnol. 2023; 41(8): 985-987.

[327]

Stoeklé HC, Ivasilevitch A, Marignac G, Hervé C. Creation and use of organoids in biomedical research and healthcare: the bioethical and metabioethical issues. Cell Adh Migr. 2021; 15(1): 285-294.

RIGHTS & PERMISSIONS

2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

AI Summary AI Mindmap
PDF

433

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/