Pluripotent Stem Cells in Disease Modelling and Drug Discovery

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2016 Jan 29

PMID 26818440

Citations 261

Authors

Yishai Avior

Ido Sagi

Nissim Benvenisty

Affiliations

Soon will be listed here.

Abstract

Experimental modelling of human disorders enables the definition of the cellular and molecular mechanisms underlying diseases and the development of therapies for treating them. The availability of human pluripotent stem cells (PSCs), which are capable of self-renewal and have the potential to differentiate into virtually any cell type, can now help to overcome the limitations of animal models for certain disorders. The ability to model human diseases using cultured PSCs has revolutionized the ways in which we study monogenic, complex and epigenetic disorders, as well as early- and late-onset diseases. Several strategies are used to generate such disease models using either embryonic stem cells (ES cells) or patient-specific induced PSCs (iPSCs), creating new possibilities for the establishment of models and their use in drug screening.

Citing Articles

Lipidomics reveals cell specific changes during pluripotent differentiation to neural and mesodermal lineages.

Odenkirk M, Jostes H, Francis K, Baker E Mol Omics. 2025; .

PMID: 40078081 PMC: 11904469. DOI: 10.1039/d4mo00261j.

Artificial intelligence-driven translational medicine: a machine learning framework for predicting disease outcomes and optimizing patient-centric care.

Abualigah L, Alomari S, Almomani M, Zitar R, Saleem K, Migdady H J Transl Med. 2025; 23(1):302.

PMID: 40065389 PMC: 11892274. DOI: 10.1186/s12967-025-06308-6.

Establishing Pancreatic Cancer Organoids from EUS-Guided Fine-Needle Biopsy Specimens.

Wang M, Gao C, Huang X, Wang M, Zhang S, Gao X Cancers (Basel). 2025; 17(4).

PMID: 40002285 PMC: 11852484. DOI: 10.3390/cancers17040692.

Human induced pluripotent stem cell-derived myotubes to model inclusion body myositis.

Canto-Santos J, Valls-Roca L, Tobias E, Garcia-Garcia F, Guitart-Mampel M, Andujar-Sanchez F Acta Neuropathol Commun. 2025; 13(1):38.

PMID: 39985015 PMC: 11844183. DOI: 10.1186/s40478-025-01933-0.

Lipidomics Reveals Cell Specific Changes During Pluripotent Differentiation to Neural and Mesodermal Lineages.

Odenkirk M, Jostes H, Francis K, Baker E bioRxiv. 2025; .

PMID: 39803501 PMC: 11722439. DOI: 10.1101/2024.12.31.630916.

References

Peters J . The role of genomic imprinting in biology and disease: an expanding view. Nat Rev Genet. 2014; 15(8):517-30. DOI: 10.1038/nrg3766. View

Yagi T, Ito D, Okada Y, Akamatsu W, Nihei Y, Yoshizaki T . Modeling familial Alzheimer's disease with induced pluripotent stem cells. Hum Mol Genet. 2011; 20(23):4530-9. DOI: 10.1093/hmg/ddr394. View

Lee G, Papapetrou E, Kim H, Chambers S, Tomishima M, Fasano C . Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature. 2009; 461(7262):402-6. PMC: 2784695. DOI: 10.1038/nature08320. View

Morris J, Wald N, Watt H . Fetal loss in Down syndrome pregnancies. Prenat Diagn. 1999; 19(2):142-5. View

Johannesson B, Sagi I, Gore A, Paull D, Yamada M, Golan-Lev T . Comparable frequencies of coding mutations and loss of imprinting in human pluripotent cells derived by nuclear transfer and defined factors. Cell Stem Cell. 2014; 15(5):634-42. DOI: 10.1016/j.stem.2014.10.002. View

Ferguson-Smith A . Genomic imprinting: the emergence of an epigenetic paradigm. Nat Rev Genet. 2011; 12(8):565-75. DOI: 10.1038/nrg3032. View

Hibaoui Y, Grad I, Letourneau A, Sailani M, Dahoun S, Santoni F . Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21. EMBO Mol Med. 2013; 6(2):259-77. PMC: 3927959. DOI: 10.1002/emmm.201302848. View

Israel M, Yuan S, Bardy C, Reyna S, Mu Y, Herrera C . Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature. 2012; 482(7384):216-20. PMC: 3338985. DOI: 10.1038/nature10821. View

Denton K, Lei L, Grenier J, Rodionov V, Blackstone C, Li X . Loss of spastin function results in disease-specific axonal defects in human pluripotent stem cell-based models of hereditary spastic paraplegia. Stem Cells. 2013; 32(2):414-23. PMC: 3947148. DOI: 10.1002/stem.1569. View

10.

Mai Q, Yu Y, Li T, Wang L, Chen M, Huang S . Derivation of human embryonic stem cell lines from parthenogenetic blastocysts. Cell Res. 2007; 17(12):1008-19. DOI: 10.1038/cr.2007.102. View

11.

Barmada S, Serio A, Arjun A, Bilican B, Daub A, Ando D . Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol. 2014; 10(8):677-85. PMC: 4106236. DOI: 10.1038/nchembio.1563. View

12.

Halevy T, Urbach A . Comparing ESC and iPSC-Based Models for Human Genetic Disorders. J Clin Med. 2015; 3(4):1146-62. PMC: 4470175. DOI: 10.3390/jcm3041146. View

13.

Ren Y, Jiang H, Hu Z, Fan K, Wang J, Janoschka S . Parkin mutations reduce the complexity of neuronal processes in iPSC-derived human neurons. Stem Cells. 2014; 33(1):68-78. PMC: 4429885. DOI: 10.1002/stem.1854. View

14.

Yang J, Cai J, Zhang Y, Wang X, Li W, Xu J . Induced pluripotent stem cells can be used to model the genomic imprinting disorder Prader-Willi syndrome. J Biol Chem. 2010; 285(51):40303-11. PMC: 3001010. DOI: 10.1074/jbc.M110.183392. View

15.

Yang J, Li Y, Chan L, Tsai Y, Wu W, Nguyen H . Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines. Hum Mol Genet. 2014; 23(13):3445-55. PMC: 4049304. DOI: 10.1093/hmg/ddu053. View

16.

Son M, Kwak J, Seol B, Lee D, Jeon H, Cho Y . A novel human model of the neurodegenerative disease GM1 gangliosidosis using induced pluripotent stem cells demonstrates inflammasome activation. J Pathol. 2015; 237(1):98-110. DOI: 10.1002/path.4551. View

17.

Urbach A, Bar-Nur O, Daley G, Benvenisty N . Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell. 2010; 6(5):407-11. PMC: 3354574. DOI: 10.1016/j.stem.2010.04.005. View

18.

Sterneckert J, Reinhardt P, Scholer H . Investigating human disease using stem cell models. Nat Rev Genet. 2014; 15(9):625-39. DOI: 10.1038/nrg3764. View

19.

Biancotti J, Narwani K, Buehler N, Mandefro B, Golan-Lev T, Yanuka O . Human embryonic stem cells as models for aneuploid chromosomal syndromes. Stem Cells. 2010; 28(9):1530-40. DOI: 10.1002/stem.483. View

20.

Huch M, Koo B . Modeling mouse and human development using organoid cultures. Development. 2015; 142(18):3113-25. DOI: 10.1242/dev.118570. View