Primary Human Organoids Models: Current Progress and Key Milestones

Overview

Journal Front Bioeng Biotechnol

Date 2023 Mar 24

PMID 36959902

Authors

Giuseppe Cala

Beatrice Sina

Paolo De Coppi

Giovanni Giuseppe Giobbe

Mattia Francesco Maria Gerli

Affiliations

Soon will be listed here.

Abstract

During the past 10 years the world has experienced enormous progress in the organoids field. Human organoids have shown huge potential to study organ development, homeostasis and to model diseases . The organoid technology has been widely and increasingly applied to generate patient-specific 3D cultures, starting from both primary and reprogrammed stem/progenitor cells. This has consequently fostered the development of innovative disease models and new regenerative therapies. Human primary, or adult stem/progenitor cell-derived, organoids can be derived from both healthy and pathological primary tissue samples spanning from fetal to adult age. The resulting 3D culture can be maintained for several months and even years, while retaining and resembling its original tissue's properties. As the potential of this technology expands, new approaches are emerging to further improve organoid applications in biology and medicine. This review discusses the main organs and tissues which, as of today, have been modelled using primary organoid culture systems. Moreover, we also discuss the advantages, limitations, and future perspectives of primary human organoids in the fields of developmental biology, disease modelling, drug testing and regenerative medicine.

Citing Articles

ECM Stiffness-Induced Redox Signaling Enhances Stearoyl Gemcitabine Efficacy in Pancreatic Cancer.

Zhao S, Agyare E, Zhu X, Trevino J, Rogers S, Velazquez-Villarreal E Cancers (Basel). 2025; 17(5).

PMID: 40075719 PMC: 11899364. DOI: 10.3390/cancers17050870.

Clinical applications of human organoids.

Verstegen M, Coppes R, Beghin A, De Coppi P, Gerli M, de Graeff N Nat Med. 2025; 31(2):409-421.

PMID: 39901045 DOI: 10.1038/s41591-024-03489-3.

Breaking the mold: 3D cell cultures reshaping the future of cancer research.

Cordeiro S, Oliveira B, Valente R, Ferreira D, Luz A, Baptista P Front Cell Dev Biol. 2024; 12:1507388.

PMID: 39659521 PMC: 11628512. DOI: 10.3389/fcell.2024.1507388.

Influence of Microenvironmental Orchestration on Multicellular Lung Alveolar Organoid Development from Human Induced Pluripotent Stem Cells.

Ozan V, Wang H, Akshay A, Anand D, Hibaoui Y, Feki A Stem Cell Rev Rep. 2024; 21(1):254-275.

PMID: 39417930 PMC: 11762634. DOI: 10.1007/s12015-024-10789-1.

Advancement and Potential Applications of Epididymal Organoids.

Nie J, Chen H, Zhao X Biomolecules. 2024; 14(8).

PMID: 39199413 PMC: 11352229. DOI: 10.3390/biom14081026.

References

Sampaziotis F, Muraro D, Tysoe O, Sawiak S, Beach T, Godfrey E . Cholangiocyte organoids can repair bile ducts after transplantation in the human liver. Science. 2021; 371(6531):839-846. PMC: 7610478. DOI: 10.1126/science.aaz6964. View

Elmentaite R, Ross A, Roberts K, James K, Ortmann D, Gomes T . Single-Cell Sequencing of Developing Human Gut Reveals Transcriptional Links to Childhood Crohn's Disease. Dev Cell. 2020; 55(6):771-783.e5. PMC: 7762816. DOI: 10.1016/j.devcel.2020.11.010. View

Liang J, Qian J, Yang L, Chen X, Wang X, Lin X . Modeling Human Thyroid Development by Fetal Tissue-Derived Organoid Culture. Adv Sci (Weinh). 2022; 9(9):e2105568. PMC: 8948548. DOI: 10.1002/advs.202105568. View

Loomans C, Williams Giuliani N, Balak J, Ringnalda F, van Gurp L, Huch M . Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential. Stem Cell Reports. 2018; 10(3):712-724. PMC: 5918840. DOI: 10.1016/j.stemcr.2018.02.005. View

van der Vaart J, Bosmans L, Sijbesma S, Knoops K, van de Wetering W, Otten H . Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves' hyperthyroidism. Proc Natl Acad Sci U S A. 2021; 118(51). PMC: 8713972. DOI: 10.1073/pnas.2117017118. View

Boretto M, Maenhoudt N, Luo X, Hennes A, Boeckx B, Bui B . Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening. Nat Cell Biol. 2019; 21(8):1041-1051. DOI: 10.1038/s41556-019-0360-z. View

Jones B, Cala G, De Coppi P, Giobbe G . Paediatric gastric organoids as a tool for disease modelling and clinical translation. Pediatr Surg Int. 2021; 37(3):317-324. PMC: 7831693. DOI: 10.1007/s00383-020-04821-x. View

Huch M, Dorrell C, Boj S, van Es J, Li V, van de Wetering M . In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013; 494(7436):247-50. PMC: 3634804. DOI: 10.1038/nature11826. View

Boretto M, Cox B, Noben M, Hendriks N, Fassbender A, Roose H . Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development. 2017; 144(10):1775-1786. DOI: 10.1242/dev.148478. View

10.

Youk J, Kim T, Evans K, Jeong Y, Hur Y, Hong S . Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2. Cell Stem Cell. 2020; 27(6):905-919.e10. PMC: 7577700. DOI: 10.1016/j.stem.2020.10.004. View

11.

Heo I, Dutta D, Schaefer D, Iakobachvili N, Artegiani B, Sachs N . Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nat Microbiol. 2018; 3(7):814-823. PMC: 6027984. DOI: 10.1038/s41564-018-0177-8. View

12.

Jung P, Sato T, Merlos-Suarez A, Barriga F, Iglesias M, Rossell D . Isolation and in vitro expansion of human colonic stem cells. Nat Med. 2011; 17(10):1225-7. DOI: 10.1038/nm.2470. View

13.

Zhang Y, Aleman J, Shin S, Kilic T, Kim D, Mousavi Shaegh S . Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc Natl Acad Sci U S A. 2017; 114(12):E2293-E2302. PMC: 5373350. DOI: 10.1073/pnas.1612906114. View

14.

Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen M . Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell. 2014; 160(1-2):299-312. PMC: 4313365. DOI: 10.1016/j.cell.2014.11.050. View

15.

Rock J, Onaitis M, Rawlins E, Lu Y, Clark C, Xue Y . Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A. 2009; 106(31):12771-5. PMC: 2714281. DOI: 10.1073/pnas.0906850106. View

16.

Giobbe G, Bonfante F, Jones B, Gagliano O, Luni C, Zambaiti E . SARS-CoV-2 infection and replication in human gastric organoids. Nat Commun. 2021; 12(1):6610. PMC: 8595698. DOI: 10.1038/s41467-021-26762-2. View

17.

Clevers H, Conder R, Li V, Lutolf M, Vallier L, Chan S . Tissue-Engineering the Intestine: The Trials before the Trials. Cell Stem Cell. 2019; 24(6):855-859. DOI: 10.1016/j.stem.2019.04.018. View

18.

Linnemann J, Miura H, Meixner L, Irmler M, Kloos U, Hirschi B . Quantification of regenerative potential in primary human mammary epithelial cells. Development. 2015; 142(18):3239-51. PMC: 4582177. DOI: 10.1242/dev.123554. View

19.

Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T . Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 2013; 499(7459):481-4. DOI: 10.1038/nature12271. View

20.

Garreta E, Kamm R, Chuva de Sousa Lopes S, Lancaster M, Weiss R, Trepat X . Rethinking organoid technology through bioengineering. Nat Mater. 2020; 20(2):145-155. DOI: 10.1038/s41563-020-00804-4. View