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Sperm Stem Cell Transplants

University of Pennsylvania veterinary researchers have figured out how to produce a continuous supply of sperm stem cells from mice, a technique that could one day be used to save endangered species or treat infertility in men.

The sperm stem cells were grown in a laboratory and implanted in infertile mice, which then went on to produce sperm and father offspring.

Researchers say the approach could work with other animals and in people. The technique could prove useful for boys and men who are undergoing cancer treatment that can make them infertile.

"The potential is very large for human infertility, particularly male infertility," said Tracy Rankin, a biologist specializing in male reproduction at the National Institute of Child Health and Human Development, which helped fund the research.

Unlike females, who are born with all the eggs they will ever have, males make sperm stem cells in their testes throughout life. At puberty, the stem cells go on to become mature sperm that can fertilize eggs.

Sperm Research

Three researchers from Penn's School of Veterinary Medicine, Ralph L. Brinster, Hiroshi Kubota and Mary R. Avarbock, reported this week in the online edition of the Proceedings of the National Academy of Sciences how they achieved the long sought-after goal of developing a line of sperm stem cells that could replicate indefinitely.

The trick was to figure out the right ingredients for concocting a culture medium that would allow the stem cells to multiply in the lab, but not have them go on to differentiate into sperm cells. The researchers zoomed in on growth factors critical to the process.

The sperm stem cells from mice were grown and maintained in the lab, then transplanted later into infertile mice. The mice started producing sperm and fathered offspring that were genetically related to the mice that supplied the stem cells.

Brinster said this technique could enable sperm stem cells from a champion racehorse to be grown indefinitely, extending the reproductive life of that animal for generations. It could also help preserve a dwindling species or extend the reproductive potential of a prized bull.

"You have immortalized that male in terms of biology," Brinster said.

The sperm stem cells could also be manipulated in the laboratory to remove a genetic defect that would have been passed along, or to add a desired trait.

"You could create better breeds, make better farm animals," said Martin Matzuk, a reproductive biology researcher at Baylor College of Medicine in Houston. Matzuk, who wrote a commentary piece to appear with the printed version of the Penn researchers' paper, said that DNA could also be tinkered with in human sperm stem cells, keeping a troublesome genetic defect from being passed along to another generation.

There are a number of possible applications for male infertility treatment.

Sperm Stem cells

Sperm stem cells could be retrieved before chemotherapy, cultured in the lab, frozen, and later reimplanted. Sperm stem cells from an infertile man might be made to proliferate in the lab and then reinserted so he could father a child naturally, Rankin said. A batch of sperm could also be produced in the lab for in vitro fertilization. About one in 10 couples is infertile, and about half the time, the man has a problem.

The knowledge of what it takes to produce sperm stem cells and go on to make sperm could lead to the development of male contraceptives, Matzuk said. The process could be blocked, stopping the production of sperm.

The Penn research also has implications for the broader field of stem-cell research, which is exploring the potential of harnessing embryonic stem cells and adult stems cells for treating Parkinson's disease and other conditions.

It is possible that sperm stem cells could be coaxed in the laboratory into becoming multipurpose stem cells similar to embryonic stem cells, Brinster said.

Paul Ellis - Men's Health