May 16, 2013
Researchers Successfully Convert Human Skin Cells Into Embryonic Stem Cells
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redOrbit Staff & Wire Reports - Your Universe OnlineResearchers at Oregon Health & Science University (OSHU) and the Oregon National Primate Research Center (ONPRC) have successfully reprogrammed human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body, a breakthrough that marks the first time human stem cells have been produced via nuclear transfer.
Stem cell therapies are believed to hold the promise of replacing cells damaged through injury or diseases such as Parkinson's and multiple sclerosis. The current work, led by Shoukhrat Mitalipov, PhD, a senior scientist at ONPRC, follows previous success in transforming monkey skin cells into embryonic stem cells in 2007.
The technique used by Dr. Mitalipov and colleagues is a variation of a commonly used method known as somatic cell nuclear transfer (SCNT). The process involves transplanting the nucleus of one cell, containing an individual's DNA, into an egg cell that has had its genetic material removed. The unfertilized egg cell then develops and eventually produces stem cells.
"A thorough examination of the stem cells derived through this technique demonstrated their ability to convert just like normal embryonic stem cells, into several different cell types, including nerve cells, liver cells and heart cells. Furthermore, because these reprogrammed cells can be generated with nuclear genetic material from a patient, there is no concern of transplant rejection," Dr. Mitalipov explained in a statement.
"While there is much work to be done in developing safe and effective stem cell treatments, we believe this is a significant step forward in developing the cells that could be used in regenerative medicine," he noted.
Another striking aspect of this breakthrough is that it does not involve the use of fertilized embryos, a topic that has been the source of considerable ethical debate.
The researchers´ success in reprogramming human skin cells came through a series of studies in both human and monkey cells. Previous unsuccessful attempts by several labs worldwide showed that human egg cells appear to be more fragile than eggs from other species. As a result, known reprogramming methods stalled before stem cells were produced.
To solve this problem, the OHSU group studied a number of alternative approaches first developed in monkey cells, and then applied them to human cells to develop a successful method.
The key to this success was finding a way to prompt egg cells to stay in a state known as "metaphase" during the nuclear transfer process. Metaphase is a stage in the cell's natural division process (meiosis) when genetic material aligns in the middle of the cell before the cell divides.
The researchers found that chemically maintaining metaphase throughout the transfer process prevented the process from stalling and allowed the cells to develop and produce stem cells.
"This is a remarkable accomplishment by the Mitalipov lab that will fuel the development of stem cell therapies to combat several diseases and conditions for which there are currently no treatments or cures," said Dr. Dan Dorsa, PhD, OHSU Vice President for Research.
"The achievement also highlights OHSU's deep reproductive expertise across our campuses. A key component to this success was the translation of basic science findings at the OHSU primate center paired with privately funded human cell studies," he added.
An important distinction in the current work is that while the method might be considered a technique for cloning stem cells, commonly known as therapeutic cloning, it would not likely be successful in producing human clones otherwise known as reproductive cloning, the researchers said.
Indeed, several years of monkey studies that utilize SCNT have never successfully produced monkey clones, and it is expected this is also the case with humans.
Furthermore, the comparative fragility of human cells is a significant factor that would likely prevent the development of clones.
"Our research is directed toward generating stem cells for use in future treatments to combat disease," said Dr. Mitalipov.
"While nuclear transfer breakthroughs often lead to a public discussion about the ethics of human cloning, this is not our focus, nor do we believe our findings might be used by others to advance the possibility of human reproductive cloning."
The research was published online May 15 in the journal Cell, and in the June 6 print edition.