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.
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)
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
EuroStem Cell 2008, iPS cells and reprogramming: turn any cell of the body into a stem cell, viewed 22 September 2015, <http://www.eurostemcell.org/factsheet/ips-cells-and-reprogramming-turn-any-cell-body-stem-cell>
http://bioscience.oxfordjournals.org/content/57/8/655.full
Cai, S., Fu, X. & Sheng, Z., 2007. Dedifferentiation: A New Approach in Stem Cell Research. BioScience, 57(8), p.655.