Hayek, Alberto
<p class="default">06:10 PM, May 10, 2006</p>
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Human Embyonic Stem Cells and Type I Diabetes: How far to the clinic?</p>
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Gillian Beattie and Alberto Hayek (Permanente Journal? Winter 2004/ Vol 8 #1.)
See Diabetes 1 folder and see Whittier folder / Winkler.</p>
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The beta cells contained within the islets of the pancreas are the only cells that exhibit appropriate glucse responsive insulin secretion.
One can transplant whole pancreases, islets, or beta cells. As of Oct 2002, full pancreatic organ xpalnts had been performed with a very high succfess rate (84% one yr survival of the
xplant) in 18,000 patients. However, only given to kidney xpalnt pts ... cuz they need life long immunosuppressives. Only abt 5000 pancreases are available for xplant annually.</p>
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The islets constitute 1% of an otherwise healthy pancreas - whose primary fxn is prodcution of digestive enzymes ... so, better to just xplant the non-functioning islets.
However, very low rate of success for this (only 11%) ... until recently ... must get rid of steroids and cyclosporin ... doing this .. and replacing them
with tacrolimus, serolimus, and daclibumab .. results in 80% insulin independence after 1 year; however you need 2-3 pancreass per patient.</p>
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Human ES stem cell therapy is the most promising.
totipotent ... can produce everything ... all three cell lines... dervied from blastocysts at in vitro fertility clinics.
they can produce ectoderm, mesoderm, and endoderm. Also they have telomerase, so they can glue telomeres back on ... maintain telomere length.
They maintain proliferative capacity.</p>
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Embyronic stem cells can either proliferate (self-renew) and differentiate or both. In culture they tend to differentiate unless prevented from doing so.
Also, they need fibroblast feeder layers for human stem cell development. Must use mouse dervied fibroblasts until recently. In Singapore, new human stem cells lines have recently been derived without exposure to mouse cells. Unfortuantely these are not permitted for use in the US (Federal law).
In summary, the requirements for self-renewal of human stem cells are unknown, but unknown factors secreted by fibroblast feeder layers are certainly crucial for maintaining pluripotency and self-renewal.
We need to elucidate the mechanisms involved in both.</p>
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Culture of human ES cells is time-consumign and difficult ... they grow as clusters or colonies and not as indiv. cells. Doubling time is 30 to 40 hours. Cells are fastididious abt conditions.
They'll either die or diffrentiate.</p>
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They tend to differnetiate spontaneously ... default path is into neurons.
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