Researchers Grow Sperm Stem Cells In Laboratory Cultures
04 Nov 2004

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 disease.

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
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Contact: Robert Bock
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301-496-5134
NIH/National Institute of Child Health and Human Development

SOURCE: Medical News Today, UK
http://tinyurl.com/48zj9

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