Race Intensifying for Clinical Application of Pluripotent Cells for Humans

Tokyo, June 7 (Jiji Press)–A Kyoto University research team said Thursday it has succeeded in creating stem cells with a greater similarity to embryonic stem cells, which can be developed into almost any tissue.

The team, led by Shinya Yamanaka, professor at the university’s Institute for Frontier Medical Sciences, calls the cells “second- generation” induced pluripotent stem (iPS) cells because it reported first-generation iPS cells in August last year.

The newly created cells have greater ES cell-like gene expression than the first-generation cells, the scientists said.

But the Japanese team was not alone, as a group at the Massachusetts Institute of Technology in Boston reported the same day that it had made similar non-embryonic stem cells with biological potency “indistinguishable from ES cells.”

The two mouse studies were published in the same electronic edition of science journal Nature, but another group of researchers from Harvard University and other U.S. institutes also reported similar achievements in Cell Stem Cell magazine the same day.

Last August, the Yamanaka group reported inducing iPS cells from mice fibroblasts through the retrovirus-mediated introduction of Oct4, Sox2, c-Myc and Klf4 transcription factors. The induced cells showed pluripotency, but they were different from ES cells in terms of gene expression patterns and have low efficiency in cell differentiation.

The study prompted researchers around the world to pursue the creation of iPS cells that can be used in place of ES cells, which have fueled a debate on ethics as they are obtained by destroying fertilized eggs and have immune reaction problems.

In the latest studies, the three teams successfully obtained the second-generation iPS cells by using “Nanog” gene expression as a marker for selection.

Compared with the Fbx15 marker used in the initial study, “Nanog is more tightly associated with pluripotency,” the Kyoto University team said.

After they were introduced into mouse eggs, mice were born with Nanog iPS cell-based tissues throughout their bodies, it reported.

But the study also showed that about 20 pct of the offspring developed tumors.

The retrovirus for the c-Myc gene introduction, or the gene itself, could be the cause of the tumor, and methods to induce Nanog iPS cells without using the retrovirus need to be developed for successful clinical application of the cells for humans, Yamanaka and his colleagues said.END

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