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FGF-signalling in the differentiation of mouse ES cells towards ...

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2008). L<strong>in</strong>eage trac<strong>in</strong>g <strong>of</strong> <strong>the</strong>se <strong>cells</strong> has not yet been performed but will elucidate whe<strong>the</strong>r <strong>the</strong><strong>in</strong>creases <strong>in</strong> β cell mass are truly by neogenesis <strong>of</strong> ductal <strong>cells</strong>. Ac<strong>in</strong>ar <strong>cells</strong> cultured <strong>in</strong> vitroshow de<strong>differentiation</strong>, possibly to <strong>the</strong> stage <strong>of</strong> <strong>the</strong> common ac<strong>in</strong>ar and endocr<strong>in</strong>e cell which isfound dur<strong>in</strong>g pancreas development. They can subsequently be re-specified <strong>in</strong>to hepatocytes <strong>in</strong>human cultures and β <strong>cells</strong> <strong>in</strong> <strong>mouse</strong> cultures, show<strong>in</strong>g a large amount <strong>of</strong> plasticity <strong>of</strong> <strong>the</strong>se<strong>cells</strong> (Lardon et al. 2004; Okuno et al. 2007).Whe<strong>the</strong>r it is possible to circumvent <strong>the</strong> patient’s auto-immune response <strong>towards</strong> <strong>the</strong>se β <strong>cells</strong> isstill to be seen. For <strong>the</strong> moment, life-long treatment with immune-suppressors represents <strong>the</strong>only alternative and is not desirable due to <strong>in</strong>herent side effects.Conclud<strong>in</strong>g remarksThe reason for putt<strong>in</strong>g a large effort <strong>in</strong>to <strong>differentiation</strong> <strong>in</strong> a 2-dimensional, serum and feederfreeprotocol is first <strong>of</strong> all to be able to better control <strong>the</strong> <strong>signall<strong>in</strong>g</strong> events go<strong>in</strong>g on <strong>in</strong> <strong>the</strong> dishand <strong>the</strong>reby better direct <strong>differentiation</strong> <strong>in</strong>to <strong>the</strong> cell types <strong>of</strong> desire. A second and not lessimportant po<strong>in</strong>t is that cell culture with animal products is not desirable due to fear <strong>of</strong> spread <strong>of</strong>disease. The latter especially has major implications <strong>in</strong> xeno-transplantations. Recently, apublication show<strong>in</strong>g derivation and culture <strong>of</strong> a xeno-free h<strong>ES</strong> cell l<strong>in</strong>e was published(Ellerstrom et al. 2006). In <strong>the</strong> future, this could very well be <strong>the</strong> only material we arecomfortable with us<strong>in</strong>g for transplantation and it will as such have major impact on <strong>the</strong>application <strong>of</strong> <strong>the</strong> various <strong>differentiation</strong> protocols applicable to cl<strong>in</strong>ical work.88

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