Scientists report first success in cloning human stem cells
Stem cells viewed on a computer screen at the University of Connecticut's Stem Cell Institute.
Ever since Ian Wilmut, an
unassuming embryologist working at the Roslin Institute just outside of
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.
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 a sperm.
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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 and Columbia University. "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, Woo Suk Hwang, a veterinary scientist at Seoul National University, 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.
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 than that contained in the nucleus of cells, and
are responsible for generating the energy needed for cells to function.
But because they lie
outside of 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.
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 1,000 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, or 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.
This article was originally published on TIME.com.
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