What is the best recipe to create specific stem cells to patients? The issue has generated years of debate and a series of contradictory documents. Ideally, the cells must develop into any cell type as well as those of a natural embryo do. For now, 7 years, the method for introducing a small set of genes in adult cells to create so-called induced pluripotent stem (iPS) dominates the field. But some researchers have stuck with an older stem cells approach to a donor nucleus into an unfertilized egg and derived from the embryo. This technique of nuclear transfer of somatic cells (SCNT) is expensive, technically difficult and heavy ethics on several fronts. But proponents argued that the cells created in this way are higher, in part because iPS cells can mature cells retain characteristics and could acquire a greater number of genetic changes in the reprogramming process. The latest research on the issue, published this week in Cell Stem Cell , examines the genetic characteristics of two types of cells and declared a tie.
This may surprise some people, because the researcher who led the work, Dieter Egli of the New York Stem Cell Foundation (NYSCF) in New York, has long been a nuclear transfer promoter. He gave an overview of the document on October 22 at the annual conference of the foundation. "This means that anyone working on iPS cells probably work with cells that are actually very good. So I have good news for you ," he told them, sparking murmurs and laughter . "What this means exactly for SCNT program, I do not know yet." Indeed, some longstanding champions of nuclear transfer Egli included-aren't ready to give up yet the method.
The discovery in 06 by Shinya Yamanaka and colleagues as inserting a few genes into mature cells could behave like immature revolutionized the field of stem cells. Labs have since refined the technique to create patient specific cells to study disease and have already started clinical trials cells derived from iPS cells to restore damaged or diseased tissue.
But some questioned whether this genetic approach to reprogramming created change himself unwanted carcinogenic mutations. "We were very worried," said Nizar Batada, a cancer biologist at the Ontario Institute for Cancer Research in Toronto, Canada. He co-authored a 2011 paper Nature showing that iPS cells had more genetic abnormalities that skin cells used to obtain them. "You have a normal cell sitting around, waiting to be a skin cell, and blasting you with genes, so there is chaotic change in DNA replication and gene expression. " Other methylation studies of DNA-adding chemical markers that control gene expression in some places-has suggested that iPS cells were some memory of their past, as adult skin cells, by example, and may be less effective to differentiate into new cell types.
Some scientists thought that the nuclear transfer method used to clone Dolly the sheep in 1996, created stem cells that are less sensitive to these issues. But there was a catch: As Yamanaka in 2012 shared the Nobel Prize in Physiology or Medicine with John Gurdon for nuclear transfer, SCNT nobody has used to create human stem cells, and the attention of the field had largely moved to iPS cells. Last year, a team led by Shoukhrat Mitalipov of Oregon Health & Science University in Beaverton finally declared success with SCNT in human cells, and the debate was revived.
Egli and colleagues wanted to know if the newly available cells really benefits held over iPS cells. Until now, most studies comparing the two methods have a common defect, Egli said: They start with derived from different donor cells. possible genetic differences between individuals make it difficult to say how reprogramming techniques change nuclear DNA.
Egli and colleagues instead used skin cells from two-a newborn and an adult to create both the SCNT stem derived cells (using donor eggs) and iPS cells. They then compared the two types of cell lines with the original cells of the skin in terms of genetic mutations, changes in gene expression, and differences in DNA methylation. Both methods resulted in about 10 mutation with respect to the average genome mature cell source. These changes do not necessarily occur during reprogramming, however, says Egli. Many were probably present in the original skin cells, and some might have arisen in the handling of cells before they have been reprogrammed.
The two types of stem cells also paid a similar amount of methylation changes. Overall, the method does not seem to matter, Egli and his team concluded. Because he is a longtime supporter of SCNT, Egli said he was "more attractive" to reveal significant differences between the two types of stem cells. "This is just not what we found."
The study says nothing about whether the changes documented in the two cell types make it less fit for use in research or therapy, Batada rating, or even if the observed mutations affect the gene activity. "That these aberrations have any function is not clear," he said, but in terms of methods of creation of two stem cells, "they are just as good or just as bad."
Mitalipov, who also contributed to the Cell Stem Cell paper, argues that nuclear transfer creates more stable cells that more closely resemble embryonic cells. It published research this summer reports that methylation patterns in nuclear transfer cells more closely mimic natural embryonic stem cells, and the ongoing work to identify other benefits.
Izpisúa Juan Carlos Belmonte, a developmental biologist at the Salk Institute for Biological Studies in San Diego, California, is the lack of differences between the two types of stem cells surprising. But this study is "probably not enough to settle this issue," he said. "There are and will always be the safety concerns [of stem cells] regardless of the method," he adds, and there is "no reason so far to discredit one for the other."
Both Egli Mitalipov and plan to continue their work on nuclear transfer and protect its value. Egli points out that research has led to other important discoveries, including technology that could allow a woman to prevent the transmission of mitochondrial diseases in children using an egg donor. And it suggests that donors of eggs-based therapies can be an easier path to regulatory approval. Until the two types of stem cells leads to an approved therapy, Egli said, "I think it would be a big mistake to put all eggs in one basket"
[
0 Komentar