A team of researchers said Wednesday that it had produced embryonic stem cells — a possible source of disease-fighting spare parts — from a cloned human embryo.
Scientists at the Oregon Health and Science University accomplished in humans what has been done over the past 15 years in sheep, mice, cattle and several other species. The achievement is likely to, at least temporarily, reawaken worries about “reproductive cloning” — the production of one-parent duplicate humans.
But few experts think that production of stem cells through cloning is likely to be medically useful soon, or possibly ever.
“An outstanding issue of whether it would work in humans has been resolved,” said Rudolf Jaenisch, a biologist at MIT’s Whitehead Institute in Cambridge, Mass., who added that he thinks the feat “has no clinical relevance.”
“I think part of the significance is technical and part of the significance is historical,” said John Gearhart, head of the Institute for Regenerative Medicine at the University of Pennsylvania. “Many labs attempted it, and no one had ever been able to achieve it.”
A far less controversial way to get stem cells is now available. It involves reprogramming mature cells (often ones taken from the skin) so that they return to what amounts to a second childhood from which they can grow into a new and different adulthood. Learning how to make and manipulate those “induced pluripotent stem” (IPS) cells is one of biology’s hottest fields.
Stem cells have the capability of maturing into different types of tissue depending on how they are stimulated. Embryonic stem cells (ESCs), plucked from a microscopic embryo, have the greatest potential. With the right molecular nudges, they could theoretically be used to grow new kidneys, lungs and hearts for use by people whose own organs have worn out.
Some experts think that “regenerative medicine” will eventually become an approach to healing that is as important as surgery or pharmacology.
The Oregon researchers, led by Shoukhrat Mitalipov, produced embryonic stem cells through “somatic cell nuclear transfer,” the technique used in 1996 to make Dolly the sheep the first cloned mammal.
The nucleus of a mature cell is transplanted into a human oocyte (egg) whose own nucleus has been removed. After the right stimulation, this new hybrid cell starts to divide and develop just as a sperm-fertilized egg would. When it is at the “blastocyst” stage — about 100 cells — its core contains a small number of embryonic stem cells capable of becoming any type of cell possessed by the human body.
But getting the doctored egg to grow even that far is extremely difficult. For some species, hundreds of eggs must be subjected to nuclear transfer before any produce viable embryonic stem cells. The failure of human oocytes to produce them had led some scientists to speculate that the technique simply might not work in people for some reason.
Mitalipov and several members of his team work at the Oregon National Primate Research Center and had refined their techniques using rhesus monkeys. They used nuclei from the skin cells of newborns or, in some cases, fetuses. Their stimulants included a pulse of electricity at the time of nuclear transfer and the addition of caffeine to the fluid cells lived in.
The tweaks and improvements apparently made all the difference. In one experiment, eight oocytes harvested from one woman produced five blastocysts and four embryonic stem cell lines — a success rate virtually unseen in other animals. The researchers subsequently proved cells were “pluripotent” by coaxing them to become, among other things, beating heart muscle cells.
The experiments were reported in a paper published online in the journal Cell.
“Where the kudos come is in being able to over time enhance and improve the technology developed in other species to make this amenable to the human oocyte,” Gearhart said.
The blastocysts could be implanted in a woman’s uterus. It might develop into a fetus. Most cloned animals, however, turn out to have major health problems and shortened lives.
“We just need to make sure it’s clear to the public that no one in their right mind would want to do that. There is no intent to do reproductive cloning. None at all,” Gearhart said.
Are these embryonic stem cells more versatile than IPS cells made by reprogramming skin cells?
“That’s of interest,” Jaenisch said. But whatever the answer, “the consequence would be to make the IPS cells better.” Given the difficulty of obtaining human oocytes, and the controversial nature of the research, embryonic stem cells aren’t likely to ever be the preferred tool of regenerative medicine, he said.