Saturday, August 12, 2006

It's Official: Adult Stem Cells to Embryonic (ethical)

The good news is that scientists are closer to being able to produce true patient-specific stem cells from non-embryonic adult somatic cells. But, we still need to stress that the research is still in its early stages.

Let's wait (but don't hold your breath) to see whether the media plays this one up as much as all the hullabaloo on unethical stem cells and the Korean veterinarian, Hwang Wu Suk's faked cloned embryonic stem cells.

Cell, one of the most respectable peer-reviewed journal covering molecular biology of the cell, has published the report of Japanese researchers who claim to have induced adult mouse fibroblast cells to revert to the embryonic stem cell stage. It's currently available at a link on this page.


Embryonic stem (ES) cells, which are derived from the inner cell mass of mammalian blastocysts, have the ability to grow indefinitely while maintaining pluripotency and the ability to differentiate into cells of all three germ layers (Evans et al., 1981; Martin, 1981). Human ES cells might be used to treat a host of diseases, such as Parkinson's disease, spinal cord injury, and diabetes (Thomson et al., 1998). However, there are ethical difficulties regarding the use of human embryos, as well as the problem of tissue rejection following transplantation in patients. One way to circumvent these issues is the generation of pluripotent cells directly from the patients' own cells.

Somatic cells can be reprogrammed by transferring their nuclear contents into oocytes (Wilmut et al., 1997) or by fusion with ES cells (Cowan et al., 2005; Tada et al., 2001), indicating that unfertilized eggs and ES cells contain factors that can confer totipotency or pluripotency to somatic cells. We hypothesized that the factors that play important roles in the maintenance of ES cell identity also play pivotal roles in the induction of pluripotency in somatic cells.

Several transcription factors, including Oct3/4 (Nichols et al., 1998; Niwa et al., 2000), Sox2 (Avilion et al., 2003), and Nanog (Chambers et al., 2003; Mitsui et al., 2003), function in the maintenance of pluripotency in both early embryos and ES cells. Several genes that are frequently upregulated in tumors, such as Stat3 (Matsuda et al., 1999; Niwa et al., 1998), E-Ras (Takahashi et al., 2003), c-myc (Cartwright et al., 2005), Klf4 (Li et al., 2005), and β-catenin (Kielman et al., 2002; Sato et al., 2004), have been shown to contribute to the long-term maintenance of the ES cell phenotype and the rapid proliferation of ES cells in culture. In addition, we have identified several other genes that are specifically expressed in ES cells (Maruyama et al., 2005; Mitsui et al., 2003).

In this study, we examined whether these factors could induce pluripotency in somatic cells. By combining four selected factors, we were able to generate pluripotent cells, which we call induced pluripotent stem (iPS) cells, directly from mouse embryonic or adult fibroblast cultures.


The researchers did not use human cells. However, other researchers have done the basic work of induction in human cells. These researchers have narrowed down the requirements, the factors for culture, for future work on human non-embryonic cells.

The stem cells form embryoid bodies in the lab and teratomas - tumors with all three of the main stem cell lines - when injected into live mice. They do not appear to be toti-potent. In other words, the scientists haven't found a way to make single celled cloned embryos.

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