I wish to express my strong doubt towards the induction claim for producing pluripotent stem cells from normal skin cells. Immediately after the publication of the Nature paper by Yamanaka?s group (Okita et al., 2007) I sent Yamanaka a Communications Arising manuscript expressing my doubt on the inductive nature of the iPS cells (Liu, 2007d) and asked him to respond. In his initial but formal response (made on behalf of all other authors) (Liu, 2007c) he admitted that ?the origin of iPS cells may be tissue stem or progenitor cells co-existing in fibroblast cultures?. As to the experiments that I proposed to him for reaching a conclusive answer on whether the iPS cells are induced from normal (differentiated) skin cells or simply the detected and expanded pre-existing stem cells, he stated that ?I agree that the experiments you[r] proposed are important.?
Unfortunately these ?important? experiments have been put aside and Yamanaka still spin heavily on his shaky induction claim. The inclusion of a sentence that ?the origin of iPS cells may be undifferentiated stem or progenitor cells? in the discussion section of their new Cell paper (Takahashi et al., 2007) is apparently an attempt to deflect criticisms rather than a sincere expression of their doubt. As a matter of fact, in their later response to me as guided by Nature, Yamanaka essentially denied the possibility of the pre-existing stem cells as the origin of the iPS cells (Liu, 2007c).
In the eyes of cloning/stem cell experts, Yamanaka?s procedure for iPS cells represents a ?Dolly?-level achievement (Wilmut and Taylor, 2007). This new study on producing human iPS cells represents another ?milestone? for cloning (Zaehres and Scholer, 2007) and even the Wright brothers? airplane for therapeutic cloning (Harris, 2007). However, I wish to say that the induction claim for pluripotent stem cells suffers from some fundamental deficiencies (Liu, 2007a; Liu, 2007b; Liu, 2007c; Liu, 2007e). Thus, I sincerely wish that Yamanaka will take a pause in further spinning on this unsubstantiated induction claim and do the important control experiments already suggested to him.

Shi V. Liu
Eagle Institute of Molecular Medicine
Apex, NC 27502, USA
SVL@logibio.com

References.

Harris, S. D. (2007). Stem cell breakthrough. MercuryNewscom http://origin.mercurynews.com/businessupdate/ci_7516801?nclick_check=1, 2007-2011-2020.
Liu, S. V. (2007a). Are iPS cells really indistinguishable from ES cells? Logical Biology 7, 66-68.
Liu, S. V. (2007b). Can the iPS airplane really fly high in the therapeutic sky? Logical Biology 7, 84-96.
Liu, S. V. (2007c). Further comments on the nature of iPS cells. Logical Biology 7, 69-72.
Liu, S. V. (2007d). iPS cells: stem cells induced from terminally differentiated cells or just pre-existing stem cells being detected? Logical Biology 7, 63-65.
Liu, S. V. (2007e). Nuclear transplatation-derived embryonic stem cells are distinct from those emerging fom fertilization. Submitted.
Okita, K., Ichisaka, T., and Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317.
Takahashi, K., Tanabe, K., Ohnuki, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell doi:10.1016/j.cell.2007.11.019.
Wilmut, I., and Taylor, J. (2007). Primates join the club. Nature.
Zaehres, H., and Scholer, H. R. (2007). Induction of pluripotency: From mouse to human. Cell 131, 834-835.


1. Further readings of collected publications on the related topics:
Stem cells (http://im1.biz/StemCell.htm or http://im1.biz/StemCell.pdf)
Cloning (http://im1.biz/Cloning.htm or http://im1.biz/Cloning.pdf)
Aging (http://im1.biz/Aging.htm or http://im1.biz/Aging.pdf)

2. List of my recent Comments posted in Nature News on cloning and iPS cells:
Safer way to make human stem-like cells revealed
http://www.nature.com/news/2007/071205/full/450775a.html
Stem cells treat anaemia in mice
http://www.nature.com/news/2007/071206/full/news.2007.347.html