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Stem cells generated from fibroblasts without use of Myc
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NEW YORK (Reuters Health) - Japanese researchers have successfully created pluripotent stem cells from mouse and human fibroblasts without using the c-Myc, which produces a transcription factor that can induce tumor formation.

In a study reported earlier this month, Dr. Shinya Yamanaka, from Kyoto University, and colleagues generated pluripotent stem cells from human dermal fibroblasts and other human somatic cells by introducing retroviruses expressing four transcription factors -- Oct3/4, Sox2, Klf4, and c-Myc.

The stem cells were morphologically similar to human embryonic stem cells and expressed embryonic stem cells markers, the authors report. The cells proliferated exponentially for at least 4 months and, under appropriate culture conditions, differentiated into all three germ layers, neural cells, and cardiac cells.

"These cells should be useful in understanding disease mechanisms, searching for effective and safe drugs, and treating patients with cell therapy," Dr. Yamanaka told Reuters Health.

In the new study, reported in the November 30th online issue of Nature Biotechnology, the researchers describe the use of a modified protocol that enabled them to create pluripotent stems without using the Myc retrovirus. This was shown using both murine and human fibroblasts.

According to the authors, this new protocol resulted in fewer non-stem cell background cells and led to stem cells that were consistently high in quality.

The use of stem cells generated without the Myc retrovirus reduced tumorigenicity. None of 26 animals given these cells developed tumors. By contrast, 6 of 37 animals given stem cells generated with the Myc retrovirus did develop tumors.

Still, the authors note that without the Myc retrovirus, the efficiency of stem cell generation is markedly reduced. "It will be important to find factors or small molecules that can enhance the efficiency of induced pluripotent stem cell generation without Myc for the generation of disease- and patient-specific induced pluripotent stem cells."

Nat Biotechnol 2007.


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