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added paragraph on addressing the tumorigenicity problem, currently adding sources
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Some recent methods have dispensed with transfection altogether, using recombinant protein growth factors instead<ref>http://masspec.scripps.edu/publications/news_art/2009_04_CellSteml.pdf</ref>.  These methods are safer for therapeutic use, as the resulting cells are much less tumorigenic than transfected iPSCs; however they are usually far less efficient than methods relying on transfection.
 
Some recent methods have dispensed with transfection altogether, using recombinant protein growth factors instead<ref>http://masspec.scripps.edu/publications/news_art/2009_04_CellSteml.pdf</ref>.  These methods are safer for therapeutic use, as the resulting cells are much less tumorigenic than transfected iPSCs; however they are usually far less efficient than methods relying on transfection.
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Regardless of the method used, the mechanism of de-differentiation is the same.  The cultured cells are induced to epigenetically reprogram themselves from a non-dividing (or slowly dividing) terminally differentiated state into an actively [[cell cycle|cycling]] pluripotent state.
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Regardless of the method used, the mechanism of de-differentiation is the same.  The cultured cells are induced to epigenetically reprogram themselves from a non-dividing (or slowly dividing) terminally differentiated state into an actively [[cell cycle|cycling]] pluripotent state<ref>http://www.bu.edu/abl/files/annual_review_gen.pdf</ref>.
    
==Applications==
 
==Applications==
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Because patient-derived iPSCs would allow for perfectly histocompatible autografts, they are preferred over ES cells by researchers working to develop stem cell therapies.  Several iPSC therapies are in clinical trials around the world (most in the United States), however none of them are currently widely available or routinely used.  The major barriers to developing iPSC therapies are the tumorigenicity of iPSCs generated using current techniques, as well as the low efficiency, labor intensiveness, and relatively high cost (compared to other modern therapies) of these techniques.  However, as researchers continue to develop better methods for producing iPSCs, it is thought that iPSC therapies for various diseases (ranging from type 1 diabetes to cardiomyopathies) will become more clinically viable.
 
Because patient-derived iPSCs would allow for perfectly histocompatible autografts, they are preferred over ES cells by researchers working to develop stem cell therapies.  Several iPSC therapies are in clinical trials around the world (most in the United States), however none of them are currently widely available or routinely used.  The major barriers to developing iPSC therapies are the tumorigenicity of iPSCs generated using current techniques, as well as the low efficiency, labor intensiveness, and relatively high cost (compared to other modern therapies) of these techniques.  However, as researchers continue to develop better methods for producing iPSCs, it is thought that iPSC therapies for various diseases (ranging from type 1 diabetes to cardiomyopathies) will become more clinically viable.
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The simplest approach to addressing the tumorigenicity problem is to screen generated iPSCs for tumorigenic mutations; however this process by itself is currently prohibitively labor-intensive and expensive.  Alternatively, some researchers have tried genetically modifying the iPSCs to make them inherently non-tumorigenic; but this approach also adds a technically difficult (not to mention, somewhat unreliable) and costly step to potential iPSC therapies.
    
Tumorigenicity of iPSCs is a real concern.  Many studies transplanting iPSC derived cells into animal models report subsequent cancer rates approaching 100% (as opposed to ~10 to 25% for grafts derived from ES cells).  Grafts from iPSCs generated using newer techniques are demonstrated to be safer, but are still generally 2 to 4 times as tumorigenic as similar grafts derived from ES cells.  Until this problem is overcome, the clinical use of iPSCs will remain reserved for treatments of "last resort".
 
Tumorigenicity of iPSCs is a real concern.  Many studies transplanting iPSC derived cells into animal models report subsequent cancer rates approaching 100% (as opposed to ~10 to 25% for grafts derived from ES cells).  Grafts from iPSCs generated using newer techniques are demonstrated to be safer, but are still generally 2 to 4 times as tumorigenic as similar grafts derived from ES cells.  Until this problem is overcome, the clinical use of iPSCs will remain reserved for treatments of "last resort".
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