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