Yes, thanks for pointing out these issues. The 1975 PNAS citation you mention is fascinating: “Thus, after almost 200 transplant generations as a highly malignant tumor, embryoid body core cells appear to be developmentally totipotent and able to express, in an orderly sequence in differentiation of somatic and germ-line tissues,many genes hitherto silent in the tumor of origin.” There is a formidable latent developmental program.

The in-vivo issues you point out related to introducing pluripotent cells are real and serious. However, I do think some progress is being made in selected areas, such as in directing differentiation of pluripotent hESCs into neural cells. A search like this one http://www.google.com/search?hl=en&q=neural+differentiation+of+embryonic+stem+cells&btnG=Search&aq=f&aqi=&aql=&oq=&gs_rfai= produces a number of relevant research citations.

“The generation of unlimited numbers of dopamine neurons from mouse embryonic stem cells can be achieved in a multi-step differentiation protocol, allowing the sequential generation of embryonic stem cells, embryoid bodies, early ectodermal cells, proliferating CNS precursors, and differentiated neurons and glia. Alternatively, neural induction and directed differentiation into various neuronal and glial cell types can be achieved by co-culture with bone marrow-derived stromal feeder cell lines such as MS5″ from http://www.mskcc.org/mskcc/html/12043.cfm

There is still a long long way to go but it should be an exciting journey.

Vince

Well, you may well be right but at my age I prefer to be an optimist. I suspect it will not be too tough to revert iPSCs in a way that they express lots of telomerase and have long telomeres like hESCs, which I think is more of a technical issue than an in-principle one. Then the question will be whether they are as reliable and ready to differentiate as ESCs. A very interesting thing covered in the second paper by Su-Chun Zhang that I mentioned is that he seems to have worked out a reliable procedure for getting pluripotent stem cells to differentiate into different neural cell types – an important feat.

On one level you are sure to be right. Whatever we know or can be done now will prove to be very crude compared to what will be known and can be done in twenty years.

Vince