The implications of cellular dedifferentiation for regenerative medicine
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Transcript of The implications of cellular dedifferentiation for regenerative medicine
The implications of cellular dedifferentiation for regenerative medicine
seminar presentation by Diaz BaiseitovBBBM 2009/2010
October 2009
BioScience Department
BC: first epigenetic concept (Aristotle)
17-18 centuries: “Homunculus” concept
18-19 centuries: Microscopy improved, return to epigenesis theory
1960s: First bone marrow stem cell transplantations by E. Donnall Thomas
1981: Embryotic stem cells isolated in mice
1998: Embryotic stem cells isolated in humans
2006: Induced pluripotent stem cells were first generated by Shinya Yamanaka's team at Kyoto University, Japan
2007: iPS from adult human cells produced by James Thomson at University of Wisconsin–Madison and Shinya Yamanaka at Kyoto University
Retrospective
Why stem cells are important?
Embryotic stem cells (ES) Pluripotent Easy to get
and operate Destruction
of embryo: moral issue
Banned in some EU countries
Amniotic fluid stem cells as an alternative
Adult (somatic) stem cells Multipotent Low chance
for immune rejection
Hard to get and isolate
Tissue specific
Not stable outside body
Transplants
Stem cell differentiation
Stem Cell
A complex mechanism driven by regulated gene expression, signaling pathways, growth factors, asymmetric cell divisions, etc.
Natural dedifferentiation Occurs in nature as stress reaction
Source: SA CAI,XIAOBING FU,AND ZHIYONG SHENG, “Dedifferentiation: A New Approach in Stem Cell Research”,
• BioScience, September2007 / Vol.57 No.8
Examples of natural regeneration
Source: Shannon J Odelberg, “Unraveling the Molecular Basis for Regenerative Cellular Plasticity”,
• PLoS Biology v.2(8); Aug 2004
Induced dedifferentiation
Done either by
SCNT or iPSC
Failure rate as
high as 95%
Ends up with: New cycle Cell death Transdifferen-
tiation
Source: Gideon Grafi “The complexity of cellular dedifferentiation: implications for regenerative medicine”,
• Trends in Biotechnology Vol.27 No.6
Implications for medicine
Differentiation: controlling genes are still unclear
Dedifferentiation: low rate of success probably
due to DNA errors and instability caused by Stress factors during sampling process that activate
retroelements in original genome (SINEs and LINEs) DNA recombination during cellular dedifferentiation Dedifferentiation gene carrying retroviral vectors that
may interfere with original genome Some of dedifferentiation genes are carcinogenic