Researchers Grow Sperm Stem Cells in Laboratory Cultures
Advance Could Lead To New Infertility Treatments, Source of Adult Stem Cells
A team of researchers working with cells from mice has overcome
a technical barrier and succeeded in growing sperm progenitor cells
in laboratory culture. The researchers transplanted the cells into
infertile mice, which were then able to produce sperm and father
offspring that were genetically related to the donor mice.
"This advance opens up an exciting range of possibilities for
future research, from developing new treatments for male infertility
to enhancing the survival of endangered species," said Duane
Alexander, M.D., Director of the NICHD.
Their research, funded in part by the National Institute of Child
Health and Human Development of the National Institutes of Health,
will be published online this week in an upcoming issue of Proceedings
of the National Academy of Sciences.
Led by Hiroshi Kubota, D.V.M., Ph.D., the team of researchers from
the University of Pennsylvania School of Veterinary Medicine in
Philadelphia, also included Mary Avarbock and Ralph L. Brinster
V.M.D., Ph.D. The researchers succeeded in developing the culture
medium containing the precise combination of cellular growth factors
needed for the cells to reproduce themselves outside the body. Known
as spermatogonial stem cells, the cells are incapable of fertilizing
egg cells but give rise to cells that develop into sperm.
In 1994, this same research team developed the means to transplant
spermatogonial stem cells from one mouse into another. The recipient
mice then produced sperm fully capable of fertilizing egg cells with
the genetic characteristics of the donor mice.
Because they can now grow spermatogonial stem cells in culture,
researchers have a ready source of cells that they could manipulate
genetically, explained the study's senior author, Ralph Brinster.
For example, researchers could implant a new gene into a spermatogonial
cell, reproduce a large number of spermatogonial cells in the culture
medium, and then implant the cells into recipient animals. These
animals could then pass the new trait on to their offspring. The
ability to introduce a new trait into animals would greatly assist
breeders of both livestock and laboratory animals.
Moreover, by culturing and freezing spermatogonial stem cells from
a valuable livestock animal or an endangered species, researchers
could extend the reproductive life of that animal indefinitely.
(The researchers developed a technique for successfully freezing
and thawing spermatogonial cells in 1996.)
By manipulating the culture media that contains the spermatogonial
stem cells, researchers might also be able to induce the spermatogonial
cells to develop into sperm cells that could be used to fertilize
eggs, providing a method to treat some types of infertility.
"This finding is likely to be applicable to humans," Dr.
Brinster said. He added that the same growth factors needed to culture
the mouse stem cells would likely foster the growth of human spermatogonial
cells as well as the cells of other mammals.
Currently, males who undergo chemotherapy that renders them infertile
can store their semen so that it can be used at a later date, should
they wish to father children. However, this approach results in
a less than 50 percent success rate. Boys who are too young to provide
a semen sample but who also need such chemotherapy treatments could
also be helped by the new technique. Their spermatogonial stem cells
could be cultured to increase their numbers, frozen, and reimplanted
at a later date, restoring their fertility.
Moreover, the new culture technique would allow researchers to further
investigate the potential of spermatogonial stem cells as a source
for more versatile adult stem cells to replace diseased or injured
tissue. The replacement tissue might be used to help patients with
spinal cord injury, or disorders like Parkinson's disease or heart
To conduct their study, Dr. Kubota and his colleagues began with
mice that had been genetically altered to express green fluorescent
protein, or GFP, which gives off a green light in the presence of
a certain wavelength of light. During key stages of the experiment,
tissue from the donor mice gave off a green light.
At the first step, the researchers could distinguish spermatogonial
stem cells from the cells used to nurture them in lab cultures by
the green light the spermatogonial stem cells gave off. (A photograph
of the spermatogonial stem cells appears at (http://www.nichd.nih.gov/new/releases/stem_cell.cfm.)
The spermatogonial stem cells also gave off green light when they
grew and reproduced in the testes of the recipient mice. Similarly,
about half of the baby mice fathered by the recipient mice also
glowed green (See photo at http://www.nichd.nih.gov/new/releases/green_brown_mice.cfm.)
Additional funding for this research was provided by the Commonwealth
and General Assembly of Pennsylvania, and the Robert J. Kleberg,
Jr. and the Helen C. Kleberg Foundation.
The NICHD is part of the National Institutes of Health (NIH),
the biomedical research arm of the federal government. NIH is an
agency of the U.S. Department of Health and Human Services. The
NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation. NICHD publications, as well
as information about the Institute, are available from the NICHD
Web site, http://www.nichd.nih.gov,
or from the NICHD Information Resource Center, 1-800-370-2943; e-mail