Modelling Human Disease with Pluripotent Stem Cells

Overview

Journal Curr Gene Ther

Publisher Bentham Science Publishers

Specialties Genetics
Pharmacology

Date 2013 Mar 1

PMID 23444871

Citations 21

Authors

Richard Siller

Sebastian Greenhough

In-Hyun Park

Gareth J Sullivan

Affiliations

Soon will be listed here.

Abstract

Recent progress in the field of cellular reprogramming has opened up the doors to a new era of disease modelling, as pluripotent stem cells representing a myriad of genetic diseases can now be produced from patient tissue. These cells can be expanded and differentiated to produce a potentially limitless supply of the affected cell type, which can then be used as a tool to improve understanding of disease mechanisms and test therapeutic interventions. This process requires high levels of scrutiny and validation at every stage, but international standards for the characterisation of pluripotent cells and their progeny have yet to be established. Here we discuss the current state of the art with regard to modelling diseases affecting the ectodermal, mesodermal and endodermal lineages, focussing on studies which have demonstrated a disease phenotype in the tissue of interest. We also discuss the utility of pluripotent cell technology for the modelling of cancer and infectious disease. Finally, we spell out the technical and scientific challenges which must be addressed if the field is to deliver on its potential and produce improved patient outcomes in the clinic.

Citing Articles

Pluripotent stem cells for target organ developmental toxicity testing.

Wu X, Chen Y, Kreutz A, Silver B, Tokar E Toxicol Sci. 2024; 199(2):163-171.

PMID: 38547390 PMC: 11131012. DOI: 10.1093/toxsci/kfae037.

Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine.

Dhanjal D, Singh R, Sharma V, Nepovimova E, Adam V, Kuca K Curr Med Chem. 2023; 31(13):1646-1690.

PMID: 37138422 DOI: 10.2174/0929867330666230503144619.

Connecting the dots: Melanoma cell of origin, tumor cell plasticity, trans-differentiation, and drug resistance.

Castro-Perez E, Singh M, Sadangi S, Mela-Sanchez C, Setaluri V Pigment Cell Melanoma Res. 2023; 36(5):330-347.

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Cell models for Down syndrome-Alzheimer's disease research.

Wu Y, West N, Bhattacharyya A, Wiseman F Neuronal Signal. 2022; 6(1):NS20210054.

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Engineering skeletal muscle tissues with advanced maturity improves synapse formation with human induced pluripotent stem cell-derived motor neurons.

Santoso J, Li X, Gupta D, Suh G, Hendricks E, Lin S APL Bioeng. 2021; 5(3):036101.

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References

Mahalingam D, Kong C, Lai J, Tay L, Yang H, Wang X . Reversal of aberrant cancer methylome and transcriptome upon direct reprogramming of lung cancer cells. Sci Rep. 2012; 2:592. PMC: 3423637. DOI: 10.1038/srep00592. View

Maehr R . iPS cells in type 1 diabetes research and treatment. Clin Pharmacol Ther. 2011; 89(5):750-3. DOI: 10.1038/clpt.2011.1. View

Reeves R, Irving N, Moran T, WOHN A, Kitt C, Sisodia S . A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat Genet. 1995; 11(2):177-84. DOI: 10.1038/ng1095-177. View

Silva G, Poirot L, Galetto R, Smith J, Montoya G, Duchateau P . Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapy. Curr Gene Ther. 2010; 11(1):11-27. PMC: 3267165. DOI: 10.2174/156652311794520111. View

Yoshizaki S, Nishi M, Kondo A, Kojima Y, Yamamoto N, Ryo A . Vaccination with Human Induced Pluripotent Stem Cells Creates an Antigen-Specific Immune Response Against HIV-1 gp160. Front Microbiol. 2011; 2:27. PMC: 3109301. DOI: 10.3389/fmicb.2011.00004. View

Ebert A, Yu J, Rose Jr F, Mattis V, Lorson C, Thomson J . Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature. 2008; 457(7227):277-80. PMC: 2659408. DOI: 10.1038/nature07677. View

Kao D, Chen S . Pluripotent stem cell-derived pancreatic β-cells: potential for regenerative medicine in diabetes. Regen Med. 2012; 7(4):583-93. DOI: 10.2217/rme.12.27. View

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

Camnasio S, Delli Carri A, Lombardo A, Grad I, Mariotti C, Castucci A . The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity. Neurobiol Dis. 2012; 46(1):41-51. DOI: 10.1016/j.nbd.2011.12.042. View

10.

Anguera M, Sadreyev R, Zhang Z, Szanto A, Payer B, Sheridan S . Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes. Cell Stem Cell. 2012; 11(1):75-90. PMC: 3587778. DOI: 10.1016/j.stem.2012.03.008. View

11.

Muller F, Schuldt B, Williams R, Mason D, Altun G, Papapetrou E . A bioinformatic assay for pluripotency in human cells. Nat Methods. 2011; 8(4):315-7. PMC: 3265323. DOI: 10.1038/nmeth.1580. View

12.

Kobayashi Y, Fukami T, Nakajima A, Watanabe A, Nakajima M, Yokoi T . Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse. Drug Metab Dispos. 2011; 40(4):671-9. DOI: 10.1124/dmd.111.043067. View

13.

Eiges R, Urbach A, Malcov M, Frumkin T, Schwartz T, Amit A . Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell. 2008; 1(5):568-77. DOI: 10.1016/j.stem.2007.09.001. View

14.

Raya A, Rodriguez-Piza I, Guenechea G, Vassena R, Navarro S, Barrero M . Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature. 2009; 460(7251):53-9. PMC: 2720823. DOI: 10.1038/nature08129. View

15.

Howell J, Wells J . Generating intestinal tissue from stem cells: potential for research and therapy. Regen Med. 2011; 6(6):743-55. PMC: 3236565. DOI: 10.2217/rme.11.90. View

16.

Friedrich Ben-Nun I, Montague S, Houck M, Tran H, Garitaonandia I, Leonardo T . Induced pluripotent stem cells from highly endangered species. Nat Methods. 2011; 8(10):829-31. DOI: 10.1038/nmeth.1706. View

17.

Sun N, Yazawa M, Liu J, Han L, Sanchez-Freire V, Abilez O . Patient-specific induced pluripotent stem cells as a model for familial dilated cardiomyopathy. Sci Transl Med. 2012; 4(130):130ra47. PMC: 3657516. DOI: 10.1126/scitranslmed.3003552. View

18.

Yoshida T, Takayama K, Kondoh M, Sakurai F, Tani H, Sakamoto N . Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection. Biochem Biophys Res Commun. 2011; 416(1-2):119-24. DOI: 10.1016/j.bbrc.2011.11.007. View

19.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

20.

Hackam D, Redelmeier D . Translation of research evidence from animals to humans. JAMA. 2006; 296(14):1731-2. DOI: 10.1001/jama.296.14.1731. View