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Regulation of Apoptosis and Differentiation by p53 in Human ...

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CHAPTER 1: Introduction<br />

1.1- HUMAN EMBRYONIC STEM CELLS<br />

The excitement <strong>and</strong> controversy surround<strong>in</strong>g the potential role <strong>of</strong> human embryonic<br />

stem cells <strong>in</strong> transplantation therapy have <strong>of</strong>ten overshadowed their potentially<br />

more important use as a basic research tool for underst<strong>and</strong><strong>in</strong>g the<br />

development <strong>and</strong> function <strong>of</strong> human tissue (Xu et al, 2002).<br />

<strong>Human</strong> embryonic stem cell l<strong>in</strong>es (hESC) are established from the <strong>in</strong>ner cell mass (ICM) <strong>of</strong> the<br />

blastocyst <strong>and</strong> differentiate <strong>in</strong>to all cell l<strong>in</strong>eages <strong>of</strong> the body (Figure 1.1). They were first derived<br />

<strong>in</strong> 1998 <strong>by</strong> James Thomson’s group <strong>in</strong> the University <strong>of</strong> Wiscons<strong>in</strong>-Madison, USA (Thomson et<br />

al., 1998) <strong>and</strong> have enormous potential as a source <strong>of</strong> cells for cell replacement therapies <strong>and</strong> as<br />

a model for early human development (H<strong>of</strong>fman <strong>and</strong> Carpenter, 2005). In fact, hESC represent a<br />

useful experimental system that provides access to stages <strong>of</strong> the human life cycle that were<br />

previously <strong>in</strong>accessible to experimentation (Pera <strong>and</strong> Trounson, 2004). Conversely, better<br />

underst<strong>and</strong><strong>in</strong>g <strong>of</strong> stem cell basic biology will help to improve ma<strong>in</strong>tenance <strong>and</strong> differentiation<br />

protocols for manipulat<strong>in</strong>g hESC, thus enabl<strong>in</strong>g the dissection <strong>of</strong> some developmental diseases<br />

<strong>and</strong> advancement <strong>of</strong> more effective treatments. Moreover, because hESC <strong>and</strong> their derivatives<br />

are diploid, they are more attractive than the transformed cell l<strong>in</strong>es for drug screen<strong>in</strong>g <strong>and</strong><br />

disease model<strong>in</strong>g.<br />

Two important features <strong>of</strong> embryonic stem cells (ESC) are their self-renewal capacity (they can<br />

be ma<strong>in</strong>ta<strong>in</strong>ed <strong>and</strong> exp<strong>and</strong>ed <strong>in</strong> culture) <strong>and</strong> pluripotency (they can differentiate to give rise to<br />

mesoderm, endoderm <strong>and</strong> ectoderm as well as germ cells). Unlike human embryonic carc<strong>in</strong>oma<br />

cell l<strong>in</strong>es (hECC, the transformed counterpart <strong>of</strong> hESC), hESC can conserve a normal karyotype<br />

if cultured under appropriate conditions.<br />

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