Researchers at Newcastle University in England report they have coaxed the first human sperm cells from embryonic stem cells, in a remarkable demonstration of how quickly the field of stem-cell science is moving.
The achievement, described in the journal Stem Cells and Development, comes just 11 years after the first human-embryonic-stem-cell line was created — an eyeblink in scientific terms — in the lab of James Thomson at the University of Wisconsin. (See the top 10 scientific discoveries of 2008.)
Although the development once again raises the specter of creating humans in a petri dish or custom-designing egg and sperm cells for reproduction, lead author Karim Nayernia says that was not his team's intention. Rather, the experiment was a proof of concept that stem cells can generate any cell in the body — not only the dozens of tissues that make up the human body but also those egg and sperm cells that may give rise to altogether new bodies. "Other cell types don't generate the next generation," says Nayernia, a professor of stem-cell biology at Newcastle University. "This makes a very big difference between our study and the study of other cell types from embryonic stem cells."
Nayernia's in vitro–derived sperm, or IVD sperm, are not exactly like naturally occurring sperm, though they do bear four important similarities to the cells created in the testes. They contain half the number of chromosomes of other human cells (somatic cells contain 46 chromosomes, but egg and sperm cells have only 23, since they combine their genetic payloads during fertilization); they possess a head and a tail; they contain proteins essential for activating the egg during fertilization; and they swim, or move as sperm do in seeking out eggs to fertilize.
On the outside, however, IVD sperm are not identical to normal sperm. "We think, for normal structure development, sperm needs the testes environment," says Nayernia. It takes 15 to 16 years in the testes before the primordial germ cells that morph into spermatogonia, or a primitive precursor of the germ cells, are able to mature into sperm cells that can successfully fertilize an egg. (See the top 10 medical breakthroughs of 2008.)
IVD sperm are not ready for transplantation into human patients — in any case, British law prohibits their transplantation into people — but they may provide valuable clues to the causes of male infertility. Nayernia's group is now working on creating sperm from the skin cells of infertile men (the sperm cells in the current study were generated from embryos discarded by fertility clinics), and by studying the way those sperm develop, researchers may gain insight into the origins of infertility and potential new treatments. Theoretically, for example, if sperm could be created from the cells of a cancer patient who is rendered infertile by chemotherapy, they could be grown in a lab and still enable him to father children.
"This area has potential powerful clinical applications mixed with people's concerns over embryo research," says Insoo Hyun, a bioethicist at Case Western Reserve University who specializes in stem-cell-related ethical issues. "All the ingredients are there for a really, really lively ethical debate."
For now, the IVD cells allow researchers to witness the normal development of sperm for the first time. "In the human, sperm development is a very long process," Nayernia says. "It takes more than 15 years and is not an accessible system. With this system, we can now watch that development in three months."
That's how long it took Nayernia's team to nurture sperm from embryonic stem cells, using a special cocktail of growth factors, nutrients and retinoic acid, a derivative of vitamin A. It is worth noting that researchers could generate IVD sperm only from male embryos; when they tried using stem cells from a female embryo, they were unable to get sperm to mature past the spermatogonial stage. That suggests that genes located on the Y chromosome, which female cells do not contain, may be essential for triggering the maturation of the primitive sperm cell.
It's unclear whether IVD sperm may eventually be able to fertilize an egg successfully — the ultimate measure of similarity between IVD sperm and normal sperm. (Nayernia is currently testing whether mouse eggs fertilized with IVD sperm can lead to a healthy animal.) If the researcher can generate human IVD sperm that look like normally developed sperm and can get the artificially created germ cells to fertilize an egg, then he can allow the resulting embryo to develop for 14 days — according to U.K. law, embryos created for research purposes must be destroyed at that point. "We would need to study that embryo before we provide any clinical applications," he says.
That might seem more like science fiction than reality, but given the pace of stem-cell research, it may not be that far off. "We have the potential therapeutic use of a technology that pushes the boundaries of what people feel comfortable with ethically," says Hyun. With more advances like this one likely to come in months if not weeks, that comfort level will have to catch up quickly.
On the outside, however, IVD sperm are not identical to normal sperm. "We think, for normal structure development, sperm needs the testes environment," says Nayernia. It takes 15 to 16 years in the testes before the primordial germ cells that morph into spermatogonia, or a primitive precursor of the germ cells, are able to mature into sperm cells that can successfully fertilize an egg. (See the top 10 medical breakthroughs of 2008.)
IVD sperm are not ready for transplantation into human patients — in any case, British law prohibits their transplantation into people — but they may provide valuable clues to the causes of male infertility. Nayernia's group is now working on creating sperm from the skin cells of infertile men (the sperm cells in the current study were generated from embryos discarded by fertility clinics), and by studying the way those sperm develop, researchers may gain insight into the origins of infertility and potential new treatments. Theoretically, for example, if sperm could be created from the cells of a cancer patient who is rendered infertile by chemotherapy, they could be grown in a lab and still enable him to father children.
"This area has potential powerful clinical applications mixed with people's concerns over embryo research," says Insoo Hyun, a bioethicist at Case Western Reserve University who specializes in stem-cell-related ethical issues. "All the ingredients are there for a really, really lively ethical debate."
For now, the IVD cells allow researchers to witness the normal development of sperm for the first time. "In the human, sperm development is a very long process," Nayernia says. "It takes more than 15 years and is not an accessible system. With this system, we can now watch that development in three months."
That's how long it took Nayernia's team to nurture sperm from embryonic stem cells, using a special cocktail of growth factors, nutrients and retinoic acid, a derivative of vitamin A. It is worth noting that researchers could generate IVD sperm only from male embryos; when they tried using stem cells from a female embryo, they were unable to get sperm to mature past the spermatogonial stage. That suggests that genes located on the Y chromosome, which female cells do not contain, may be essential for triggering the maturation of the primitive sperm cell.
It's unclear whether IVD sperm may eventually be able to fertilize an egg successfully — the ultimate measure of similarity between IVD sperm and normal sperm. (Nayernia is currently testing whether mouse eggs fertilized with IVD sperm can lead to a healthy animal.) If the researcher can generate human IVD sperm that look like normally developed sperm and can get the artificially created germ cells to fertilize an egg, then he can allow the resulting embryo to develop for 14 days — according to U.K. law, embryos created for research purposes must be destroyed at that point. "We would need to study that embryo before we provide any clinical applications," he says.
That might seem more like science fiction than reality, but given the pace of stem-cell research, it may not be that far off. "We have the potential therapeutic use of a technology that pushes the boundaries of what people feel comfortable with ethically," says Hyun. With more advances like this one likely to come in months if not weeks, that comfort level will have to catch up quickly.
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