Induced Pluripotent Stem Cell (iPSC) has opened up new approaches in disease modeling, personalized medicine, cell therapy, regenerative medicine and so on.
2. 12 years of iPSC
Dr. Shinya Yamanaka Dr. Kazutoshi Takahashi
Adapted from Bob Argiropoulos Slide
3. Objectives
Understand the advantages of
using iPSC for disease modelling
Know how iPS cells are used in
disease modeling
Realize the possibilities of hiPSC
in future disease modeling
7. Models Species
• Different pathophysiology and
genetic factors
iPSC: “Disease in vitro”
Having individual’s unique genotype
precisely (almost)
Image: Vera and Lorenz Development 142 18 (2015)
10. Alzheimer’s Disease in-vitro
• Are they showing secretion of Aβ Peptite, Oligomers?
• Can we simulate toxicity and cell death?
Do they contain disease genotype & phenotype?
16. Stress & Cell Death
Kondo, T. et al. Cell Stem Cell (2013).
17. Alzheimer’s Disease in-vitro
• Are they showing secretion of Aβ Peptite, Oligomers?
• Can we induce toxicity and simulate cell death?
Do they contain disease genotype & phenotype?
18. Challenges
• Variations in differentiation efficiency [Miura, K. et al. (2009), Koyanagi-Aoi, M. et al. (2013)]
• Choose truly pluripotent iPSC [Takahashi, K. & Yamanaka (2016)]
• Line-to-line variations in the maturation of differentiated cells
• Culture condition [Inoue, H. et al. (2014)]
• microRNA switch [Miki, K. et al. (2015)]
23. References
1. Ardhanareeswaran, K., Mariani, J., Coppola, G., Abyzov, A. & Vaccarino, F. M. Human induced pluripotent stem cells for modelling neurodevelopmental disorders. Nat. Rev.
Neurol. 13, 265–278 (2017).
2. Chen, Y.-W. et al. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat. Cell Biol. 19, 542–549 (2017).
3. Dutta, D., Heo, I. & Clevers, H. Disease Modeling in Stem Cell-Derived 3D Organoid Systems. Trends Mol. Med. 23, 393–410 (2017).
4. Ebert, A. D., Liang, P. & Wu, J. C. Induced pluripotent stem cells as a disease modeling and drug screening platform. J. Cardiovasc. Pharmacol. 60, 408–16 (2012).
5. Kondo, T. et al. Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 12,
487–96 (2013).
6. Li, L., Chao, J. & Shi, Y. Modeling neurological diseases using iPSC-derived neural cells. Cell Tissue Res. 371, 143–151 (2018).
7. Liu, C., Oikonomopoulos, A., Sayed, N. & Wu, J. C. Modeling human diseases with induced pluripotent stem cells: from 2D to 3D and beyond. Development 145, dev156166
(2018).
8. Shaheen, N., Shiti, A. & Gepstein, L. Pluripotent Stem Cell-Based Platforms in Cardiac Disease Modeling and Drug Testing. Clin. Pharmacol. Ther. 102, 203–208 (2017).
9. Shi, Y., Inoue, H., Wu, J. C. & Yamanaka, S. Induced pluripotent stem cell technology: a decade of progress. Nat. Rev. Drug Discov. 16, 115–130 (2017).
10. Siller, R., Greenhough, S., Park, I.-H. & Sullivan, G. J. Modelling human disease with pluripotent stem cells. Curr. Gene Ther. 13, 99–110 (2013).
11. Takahashi, K. et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861–72 (2007).
12. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–76 (2006).
13. Workman, M. J. et al. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat. Med. 23, 49–59 (2017).
Editor's Notes
recap in short:
We pull out Adult somatic cell.
We introduce 4 Reprogramming Factors.
We got stem cell with pluripotency
Isolation is critical
Astrocytes
Cardiomyocytes
Personalized Disease Modeling
Amyloid Precursor Protein (APP)
Secreted amyloid precursor protein β
Differentiation: one of the critical stage cell fate
Beta amyloid peptide
Amyloid Precursor Protein (APP)
Secreted amyloid precursor protein β
Differentiation: one of the critical stage cell fate
CRISPR reprogramming instead of 4 RF (Article Presentation)
microRNA switch: activation/deactivation of different microRNA to control the cell culture
Successful simulation of complex neural interaction. Simulated impaired intestinal-enteric nervous system (ENS) to model Hirschsprung disease (problem passing stool)
lung bud organoids (LBOs) development. Able to model in vitro virus infection which is causal for airway obstruction in infants, pulmonary fibrosis, couple of other lung disease