1. In the name of
god

2. Click to edit Master subtitle style
Induced pluripotent
stem cells
IPSCs
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3. Stem Cells
The importance of this cell type is that it can self-renew and differentiate

4. 3 Types of Stem Cells, Based on Differentiation Potential
As you start to learn about stem cells, one of the most common questions to have is, “What types of stem cells exist?
3 Types of Stem Cells, Based on Differentiation Potential
Unipotent Stem Cells Spermatogonial
Multipotent Stem Cells Hematopoietic
Pluripotent Stem Cells Embryonic Stem cells

5. 3 Types
of Stem Cells

6. Embryonic Stem cells
Among the natural pluripotent stem cells, embryonic stem cells are the best example
into any of the three germ layers, which are: ectoderm, endoderm and mesoderm. These three germ layers further differentiate to form all tissues and organs within a human being

7. Applications of Embryonic stem
Embryonic stem (ES) cells are widely used for different purposes, including gene targeting, cell therapy,
tissue repair, organ regeneration,

8. Cleavage This cells are obtained from different sources
Zygote
Blastocyst
with blastocoele cavity

9. Therapeutic cloning

10. have been restricted to used ES cell
by ethical issues regarding cell sources
Immunological rejection in cell therapy

11. 1962
NUCLEAR REPROGRAMMING TO A PLURIPOTENT STATE BY THREE APPROACHESSHINYA YAMANAKA & HELEN M. BLAUNATURE|VOL 465|10 JUNE 2010|DOI: /NATURE09229

12. SHINYA YAMANAKA,A SENIOR INVESTIGATOR AT THEGLADSTONE INSTITUTES—WHICH IS AFFILIATED WITH UCSF —HAS WON THE 2012 NOBEL PRIZE IN PHYSIOLOGY OR MEDICINE FOR HIS DISCOVERY OF HOW TO TRANSFORM ORDINARY ADULT SKIN CELLS INTO CELLS THAT, LIKE EMBRYONIC STEM CELLS, ARE CAPABLE OF DEVELOPING INTO ANY CELL IN THE HUMAN BODY.

13. iPS cells were first produced from mouse cells in 2006 and human cells in 2007 and are tissue-specific cells that can be reprogrammed to become functionally similar to embryonic stem cells.

14. human iPS cells resemble human ES cells in many aspects, such as morphology, proliferation, pluripotency
markers, gene expression profiles, epigenetic
status, and differentiation potential

16. Oct3/4: Sox2: Essential for embryonic development
Involve in the maintenance of self renewal.
Repression in ES cells leads to the formation trophoectoderm
Sox2:
Essential for embryonic development
Downregulation by siRNA silencing leads
to the differentiation of in cell murine ES cells

17. Klf4
Klf4 repress p53 directly,p53 protein suppress Nanog during ES cell differentiation, Klf4 contributes to activation of Nanog and other ES cell-specific genes
c-Myc
the role of c-Myc has been highlighted as a possible master regulator of pluripotency

18. Methods for Delivery of Reprogramming factors
Viral Methods:
Integrating Viruses : Lentivirus & Retrovirus
Non-integrating Viruses : Adenovirus,
Sendai Virus
Non-viral Methods:
Protein transfection
mRNA transfection
miRNAtransfection
miR-302/ 367
miR- 17
Vectors
non-integrating
excisable
chemical compounds

21. Identification of ips cells

22. morphology,
proliferation
Profiling
The formation of teratomas
Chimera formation
Tetraploid complementation

23. Mouse ES (a) and iPS (b) cells form dome-shaped, refractile colonies
Mouse ES (a) and iPS (b) cells form dome-shaped, refractile colonies. These colonies are in contrast to the flat morphology of mouse epiblast-derived stem cells (f), which resemble human ES (d) and iPS (e) cells

28. iPS cells were
first produced from
human cells in 2007

30. Nanog
In embryonic stem cells, Nanog, along with Oct-3/4 and Sox2, is necessary in promoting pluripotency.
LIN28
LIN28 is an mRNA binding protein expressed in embryonic stem cells and embryonic carcinoma cells associated with differentiation and proliferation. (Thomson et al.)

31. These issues limit the wide application of iPS cells
human iPS cells are normally derived from dermal fibroblasts because of their accessibility and relatively high reprogramming efficiency
These issues limit the wide application of iPS cells
During skin biopsy, the exposure of the dermis to ultraviolet light might increase the risk for chromosomal aberrations. In addition, it cannot be ignored that patients would experience the pain and the risk of infection when obtaining dermal fibroblasts

32. Blood cells are the most easily accessible source
it is not need to maintain cell cultures extensively prior to reprogramming experiments
The venipuncture is safer than skin biopsy
Numerous peripheral blood samples have already been frozen
and stored in blood banks

33. The reprogramming of peripheral blood cells
started with research on mice in 2008.
utilized retroviral-mediated factors
(Oct3/4,Klf4, Sox2, and c-Myc)
to reprogram mouse B and T lymphocytes.
Hong et al. (2009) generated
iPS cells from mouse T lymphocytes
by the introduction of Oct3/4, Sox2,
Klf4, and c-Myc.

34. After mouse peripheral blood cells were
reprogrammed,Haase et al. (2009)
generated human iPScells from cord blood
(CB). It is an advantage that CB can be
obtained from public and commercial CB
banks without any risk to donors.
the use of CB is still limited because
it can only be obtained from neonates.

35. Loh et al. (2010) separated Mononuclear cells (PBMCs) and CD34+ cells (PBCD34+) from peripheral blood samples
Staerk et al. (2010) utilized a doxycycline-inducible lentivirus construct to derive iPS cells from T lymphocytes and Myeloid cells
reprogramming efficiency of T lymphocytes was higher than that of myeloid cells
higher proliferation
better long-term growth potential

37. Disease modeling

38. Up to now, iPS cells have had main applications
in three major areas: human disease modeling (Zhang
et al., 2012), regenerative medicine, and drug discovery

41. IPS CELLS TO CURE SC ANEAMIA

42. Ips cell reprogramming: problems
Low efficiency of reprogramming
As using of retroviruses for induction of factor can lead to mutation and cancer
Rich of tumors formation
Efficient differentiation protocols required