Scientists Report First Success in Cloning Human Stem Cells

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It’s been 17 years since Dolly the sheep was cloned from a mammary cell. And now scientists applied the same technique to make the first embryonic-stem-cell lines from human skin cells.

Ever since Ian Wilmut, an unassuming embryologist working at the Roslin Institute just outside Edinburgh stunned the world by cloning the first mammal, Dolly, scientists have been asking: Could humans be cloned in the same way? Putting aside the ethical challenges the question raised, the query turned out to involve more wishful thinking than scientific success. Despite the fact that dozens of other species have been cloned using the technique, called nuclear transfer, human cells have remained stubbornly resistant to the process.

Until now. Shoukhrat Mitalipov, a professor at Oregon Health & Science University, and his colleagues report in the journal Cell that they have successfully reprogrammed human skin cells back to their embryonic state. The purpose of the study, however, was not to generate human clones but to produce lines of embryonic stem cells. These can develop into muscle, nerve or other cells that make up the body’s tissues. The process, he says, took only a few months, a surprisingly short period to reach such an important milestone.

(MORE: Stem-Cell Research: The Quest Resumes)

Nuclear transfer involves inserting a fully developed cell — in Mitalipov’s study, the cells came from the skin of fetuses — into the nucleus of an egg, and then manipulating the egg to start dividing, a process that normally only occurs after it has been fertilized by sperm. After several days, the ball of cells that results contains a blanket of embryonic stem cells endowed with the genetic material of the donor skin cell, which have the ability to generate every cell type from that donor. In Dolly’s case, those cells were allowed to continue developing into an embryo that was then transferred to a ewe to produce a cloned sheep. But Mitalipov says his process with the human cells isn’t designed to generate a human clone, but rather just to create the embryonic stem cells. These could then be manipulated to create heart, nerve or other cells that can repair or treat disease.

“I think this is a really important advance,” says Dieter Egli, an investigator at the New York Stem Cell Foundation. “I have a very high confidence that versions of this technique will work very well; it’s something that the field has been waiting for.” Egli is among the handful of scientists who have been working to perfect the technique with human cells and, in 2011, succeeded in producing human stem cells, but with double the number of chromosomes. In 2004, Hwang Woo-suk, a veterinary scientist at Seoul National University, had claimed to have succeeded in achieving the feat, but later admitted to faking the data. Instead of generating embryonic-stem-cell lines via nuclear transfer, Hwang’s group produced the stem cells from days-old embryos, a technique that had already been established by James Thomson at University of Wisconsin in 1998.

That scandal, as well as ethical concerns about the dangers of encouraging work that could lead to human cloning, dried up interest in getting the process to work with human cells. Then came a breakthrough in 2007, when Shinya Yamanaka of Kyoto University succeeded in reprogramming adult skin cells back to their embryonic state simply by dousing them in a concoction of four genetic factors and some growth media. That technique for generating embryonic-like stem cells (called induced pluripotent stem cells, or iPS cells) bypassed the need for transferring the cells into eggs, as Wilmut had done, and also averted the ethical issues attached to extracting stem cells from embryos as Thomson had done. Plus, the iPS cells had the advantage that patients could generate their own stem cells and potentially grow new cells they might need to treat or avert diseases like diabetes, Alzheimer’s or heart problems.

Except that researchers still couldn’t prove that the heart, nerve, muscle and other cells they made from the iPS cells were exactly like the ones generated from the embryonic stem cells. The gold standard embryonic stem cells still came from embryos themselves, including ones that were made through nuclear transfer.

(MORE: Stem-Cell Miracle? New Therapies May Cure Chronic Conditions Like Alzheimer’s)

Now that the technique appears to work with human cells, the process could be another source of generating stem cells that may ultimately treat patients, says Mitalipov. His group is especially interested in promoting the technique for treating mitochondrial diseases — these organelles posses a different set of DNA from that contained in the nucleus of cells, and are responsible for generating the energy needed for cells to function. But because they lie outside the nucleus, transferring cells from a patient with mitochondrial diseases into a donor egg that has a healthy set of mitochondrial DNA would generate populations of cells that are free of disease.

In order to make the process work, Mitalipov says he modified more than a dozen steps in the process that proved successful with sheep and other species. His group had the advantage of working first with monkey eggs; the knowledge about what stimulated the eggs to start dividing helped him to make the appropriate changes in the human eggs that contributed to his success.

Beginning with high-quality eggs that were donated by healthy volunteers was critical, he says. Most previous attempts involved discarded eggs from IVF clinics that may have been of lesser quality and affected their ability to survive the transfer process. From the monkey studies, the team also realized that the process of introducing the donor cell into the egg also required a gentle touch; timing the transfer at the point when the egg was most likely to accept the new genetic material and start dividing was important. Infusing a bit of caffeine into the process also helped. “Even though nothing we did seems that brand new — there wasn’t anything that people didn’t try in other species or we haven’t tried with monkey cells — but the right combination, timing and concentration made the difference,” says Mitalipov.

(MORE: The Stem-Cell Ruling: Scientists Alarmed at ‘Step Backward’)

He estimates that about 50% of the success can be attributed to the quality of the eggs while the remaining 50% is related to the optimization of the process. So far, the technique appears to be pretty efficient; from eight eggs, the group generated four embryonic stem-cell lines. In the future, Mitalipov anticipates it will be possible to produce a stem-cell line from each donated egg. “We knew the history of failure, that several legitimate labs had tried but couldn’t make it work,” he says. “I thought we would need about 500 to 1000 eggs to optimize the process and anticipated it would be a long study that would take several years. But in the first experiment we got a blastocyst, and within a couple of months we already had [an embryonic] stem-cell line. We couldn’t believe it.”

Egli and other stem-cell scientists are eager to replicate the process, to test how reliable and robust it is, and hurdles still remain before the technique is standardized. It’s not clear yet, for example, whether the process will work as efficiently with adult — older — cells, and healthy egg donors may not be as available in some parts of the country as they were in Oregon, where the state allows scientists to compensate donors for their eggs, just as IVF clinics do. But the achievement could establish another important source of stem cells that patients can generate to ultimately treat themselves.

MORE: Stem-Cell Scientists Awarded Nobel Prize in Physiology or Medicine

17 comments
Nirali
Nirali

Scientists have been trying to obtain stem cells from cloned human embryos for more than a decade, without success. It's understood that in previous attempts, the embryos stopped developing before producing the cells.

happyupdates
happyupdates

hi, First, these are not embryonic stem cells.  That is not clear in your first sentence.  Second, I stopped reading when you said that you they put a cell into a nucleus.  You don't put a cell into a nucleus.  You put a nucleus into a cell Results.  And this is not a matter of semantics.  It is a matter of the author's credibility - she wrote a book on stem cells? 

ShilpaHirani
ShilpaHirani

The power of humanity to produce cloned human cells for scientific purposes is incredible, but not necessarily ethical. While no one needs to fear clone armies; we ought to fear our ability to create and destroy human life on demand without thinking for the sake of scientific or medical advancement. Many within the scientific community and without hold that human life should never be created or destroyed as means to any end. http://resultplanet.org

michaelshih
michaelshih

2002,I left Biocarta to work at ITRI Research Institute at Taiwan,
Early Oct My mother pass away at San Diego, End of Oct,
I participated running exercise at ITRI, I fall down, I saw my
mother, She told me " It is not the time for you to come here,
go back!" I also saw my brother in law, two uncles, and
grandma! Few days later, I was moved to major hospital at Taipei!
One night, I waked up, and knell down against the window .
my wife ask me "What you doing?" I told her : I saw  Jesse

mkb
mkb

Do we Need cloning at all? Darwin,s Theory says survival of the fittest 

Look at this way, It is not just the survival of the fittest, it is making our each and every organ  and cells to be fit so that survival of all organs become fit and every individual survives

Improve Physical Intelligence of all cells and organs.

Make all our body cells do their work properly

This can be achieved Pl visit http://mkbperfecthealth.blogspot.in/

Walking and working are the major dynamic attributes of Human being 

If you use more of your brain You are called Inteligent

if you use more of your muscles you are called Not iteligent

But Humans are evolved by millions of years of evolution

Muscles and bones and their work gives stimulus to all other vital organs

working of the muscles and bones manages our carbohydrates, fats and proteins.

Learn right walking for better living

Pl visit http://www.ebay.com/itm/MKB-Perfect-Walking-Patent-Pending-Invented-shoes-/230982805476?pt=US_Men_s_Athletic_Footwear&hash=item35c7a5e7e4

Re invnet walking and live long 

PiyushPatel
PiyushPatel

this is a big successful by scientist..

i wish it might be helping to create a new organ which is damaging in human body... it is a great success...

http://indeduworld.com/

donthateme87
donthateme87

My life is meaningless as long as you're still alive. What am I while you exist? A shadow? An echo?

Star Trek Nemesis

RoseTherese
RoseTherese

"Putting aside the ethical challenges the question raised . . . ." --blah, blah, blah.

Once again, the "we can do this" enthusiasts fail to consider the more important ". . . should we?" This is more dehumanizing news than even the Gosnell case, as it takes humanity another step further from humanity. At it's core, this is slavery, removing freedom from humans and putting them completely at the behest of thier human master. These scientists are not creating "stem cell lines" they are creating human embryos. Forget Brave New World, we don't have to look that far back; this is more The Matrix, in which human beings were essentially turned into "batteries" here, human beings are first turned into "medicine" then what . . . eventually where does this lead -- oh, yeah, probably something along the lines of Brave New World. Stupidity. Really.

ddmagee57
ddmagee57

oh!  That really clears things up!  Everyone misunderstands, so they interpret the facts as they wish to argue their gut opinion.  You'd rather be unarguable than clear, I guess.

Peace_2_All
Peace_2_All

Yay... hopefully some steps that haven't been thwarted by the far-right wingers.  

Peace...

aliberaldoseofskepticism
aliberaldoseofskepticism

This would be awesome, but you made so many mistakes. How do you put a cell in a nucleus? You can put a nucleus in a cell, but putting a cell in a nucleus isn't the same thing.

Pro-lifers will no doubt object. I say the true horror of Parts: The Clonus Horror was the dude in the speedo, though.

Mahaa
Mahaa

First, these are not embryonic stem cells.  That is not clear in your first sentence.  Second, I stopped reading when you said that you they put a cell into a nucleus.  You don't put a cell into a nucleus.  You put a nucleus into a cell.  And this is not a matter of semantics.  It is a matter of the author's credibility - she wrote a book on stem cells? 

scott889
scott889

could negate whole papers findings...

hsknyc
hsknyc

@Mahaa 

im no scientist, but I think u have to put the old cell(DNA/info?) into the nucleus of the new cell to manipulate cell growth.  Im seriously talking out of my ass.

aliberaldoseofskepticism
aliberaldoseofskepticism

Nuclei are inside cells. Normal cloning of mammals consists of removing the nucleus from the ovum, putting a (diploid) donor nucleus in that same ovum, and simulating fertilization.