Dedifferentiation is a term used to suggest that differentiated epithelial cells revert to a previous developmental stage before their subsequent differentiation into an alternative cell fate. Hereby we discuss about the phenomenon and their impact in medical applications.

1. Dedifferentiation
Presented by
Hang Jie Justin
Izz Hariz Por Kwang
Jeff Zoe

2. Introduction
O Dedifferentiation is an important biological phenomenon:
Cells regress from a specialized function to a simpler
state reminiscent of stem cells
O Stem cells that are derived by dedifferentiation could be
a new resource for regenerative medicine (poses no risk
of genetic incompatibility or immune rejection)
O It also offers an ethically acceptable alternative route to
obtain an abundant source of stem cells compare than
the use of stem cells derived from embryonic tissue
- (CAI et al.
2007)

3. How to reprogram stem cells?
O Experimented by - Takahashi and Yamanaka
O Introduce four genes (Oct-3/4, Sox2, c-Myc,
and KLF4) into an adult mouse fibroblast
population
O Generate colonies with the characteristics of
ESCs
O Colonies were capable of differentiation to
endodermal, ectodermal, and mesodermal
lineages after transplant in immunodeficient
mice
- (Friedmann-Morvinski & Verma
2014)

4. - (EuroStemCell 2012)

5. Phenomenon of Dedifferentiation
O The phenomenon can be observed at the
level of :
O Genetic - cell undergoes reversion to
progenitor cell gene expression profile
O Protein - evidenced by the up-regulation of
progenitor & down-regulation of differentiated
cell related proteins
O Morphology - dedifferentiated cells are
smaller, fewer organelles and have high
karyoplasmic ratio
O Functional - cells regains the capacity to
proliferate
- (CAI et al.
2007)

6. Medical Application & Research
1. To study neurological diseases
O Obtain the neurons from patient through
dedifferentiation of their skin cells and
reprogram them into affected neurons
O Thus able to further work on the affected
neurons by searching and testing new
drugs to treat or protect patients against
the disease
- (EuroStemCell 2012)

7. 2. Dedifferentiation of epithelial
cells for corneal maintenance:
O Stem cells in corneal limbus
forming a ring of tissue
around the central cornea,
and epithelial cells in the
central areas
O After proliferating, stem cells
differentiate into terminal
corneal epithelial cells that
replace the cells shed in the
central cornea
- (Yoon et al. 2014)

8. 3. Treatment of Osteoarthritis
O Technique developed by - Dr Paul
Genever
O To revitalize cells from older people with
osteoarthritis to repair worn or damaged
cartilage, therefore reducing pain
O Cultivated spheroid clusters of cells in tiny
cavities, by using pharmaceutical to
induce cell-self-eating effects and
consequently reduce in size, which
stimulate dedifferentiation and the cells
revert to embryonic state
- (Alexandra Thompson 2015)

9. Current Medical development
-Clinical Stages
O Masayo Takahashi, has been using induced
pluripotent stem (iPS) cells to prepare a
treatment for age-related macular
degeneration.
O Skin cells taken from people with the disease
and converted them to iPS cells.
O Coax these cells to become retinal pigment
epithelium cells, and then to grow into thin
sheets that can be transplanted to the
damaged retina.
- (Cyranoski 2014)

10. Safety test
O Researches has been done on iPS cells in
monkey and there is no immune reaction
found.
O There have been concerns that iPS cells
could cause tumours, but Takahashi's
team has found that to be unlikely in
mice and monkeys.
- (Cyranoski 2014)

11. Future Application
O Cartilage injury remains a challenge in
orthopedic surgery due to the fact that
articular cartilage has limited capacity for
intrinsic healing.
O The main cells in the cartilage are the
chondrocytes. When they dedifferentiate, the
tend to lose their bone like characteristics.
O To generate more chondrocytes for studies,
there will have to be a dedifferentiation of
chondrocytes.
- (Wei et al. 2012)

12. Future Application
O Therefore through the dediffrentiation of
chondrocytes, studies on redifferentiation
of chondrocytes can be carried out.
O Successful redifferentiation of
chondrocytes can be used in replacing the
dedifferentiated chondrocytes in the
bones to improve the rate of cartilage
healing.
- (Lin et al. 2008)

13. Limitation in
Dedifferentiation Process
O High medical cost
O Lack of large-scale culture technologies
O Longer timeframe needed to prepare the
cells for transplantation (eg: crucial spinal
cord injuries)
O Impractical to isolate neurons directly from
a patient’s brain
O Cells isolated from the patient will be
affected and have a little therapeutic value

14. O Low quality of cells which derived from
somatic cells of aged individuals
(incidence of spontaneously occurring tumors)
O Integration site of retroviral vectors and also
the use of undefined serum-containing media
to support IPSC generation will increase the
risk of insertional mutagenesis and the risk of
tumorigenicity
O The use of oncogenic transgenes, such as
MYC gene (code for transcription factor), can
also increase the risk of tumour development
Limitation in
Dedifferentiation Process

15. Conclusion
O Cell dedifferentiation is an important part
of the life of a cell and is an important part
of medical research
O More research towards the
dedifferentiation of cells are needed to be
carried out to ensure that the
dedifferentiation pathways are fully
understood

16. References
O Alexandra Thompson 2015, Researchers develop dedifferentiation
technique to help treat osteoarthritis, viewed on 26th September 2015,
<https://www.regmednet.com/users/1034-alexandra-
thompson/posts/2947-researchers-develop-dedifferentiation-technique-
to-help-treat-osteoarthritis#>
O CAI, S., FU, X. & SHENG, Z., 2007. Dedifferentiation: A New Approach
in Stem Cell Research. BioScience, 57(8), p.655, viewed on 26th
September 2015,
<http://bioscience.oxfordjournals.org/content/57/8/655>
O Cyranoski, D 2014, Next-generation stem cells cleared for human trial,
Nature, viewed on 26th September 2015,
<http://www.nature.com/news/next-generation-stem-cells-cleared-for-
human-trial-1.15897>
O EuroStemCell 2012, IPS cells and reprogramming: turn any cell of the
body into a stem cell, viewed on 26th September 2015,
<http://www.eurostemcell.org/factsheet/ips-cells-and-reprogramming-
turn-any-cell-body-stem-cell>
O Friedmann-Morvinski, D. & Verma, I.M., 2014. Dedifferentiation and
reprogramming: origins of cancer stem cells. EMBO reports, 15(3),
pp.244–53, viewed on 26th Semptember 2015,
<http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3989690&to
ol=pmcentrez&rendertype=abstract>

17. O Lin, Z. et al., 2008. Gene expression profiles of human
chondrocytes during passaged monolayer cultivation.
Journal of Orthopaedic Research, 26(9), pp.1230–1237
O Wei, Y. et al., 2012. Chondrogenic differentiation of induced
pluripotent stem cells from osteoarthritic chondrocytes in
alginate matrix. European cells & materials, 23, pp.1–12,
viewed on 26th September 2015,
<http://www.ncbi.nlm.nih.gov/pubmed/22241609>
O Yoon, J.J., Ismail, S. & Sherwin, T., 2014. Limbal stem cells:
Central concepts of corneal epithelial homeostasis. World
journal of stem cells, 6(4), pp.391–403, viewed on 26th
September 2015,
<http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=
4172668&tool=pmcentrez&rendertype=abstract>
References

18. Thank You 