An injection of banked sperm-producing stem
cells can restore fertility to male primates who become sterile due to cancer
drug side effects, according to researchers at the Univ. of Pittsburgh School of
Medicine and Magee-Womens Research Institute.
In their animal study, which was published in Cell Stem Cell, previously
frozen stem cells restored production of sperm that successfully fertilized
eggs to produce early embryos.
Some cancer drugs work by destroying rapidly
dividing cells. As it is not possible to discriminate between cancer cells and
other rapidly dividing cells in the body, the precursor cells involved in
making sperm can be inadvertently wiped out leaving the patient infertile, says
senior investigator Kyle Orwig, associate professor, Department of Obstetrics,
Gynecology and Reproductive Medicine, Pitt School of Medicine.
"Men can bank sperm before they have
cancer treatment if they hope to have biological children later in their
lives," he says. "But that is not an option for young boys who
haven't gone through puberty, can't provide a sperm sample, and are many years
away from thinking about having babies."
Even very young boys, though, have
spermatogonial stem cells in their testicular tissue that are poised to begin
producing sperm during puberty. To see whether it was possible to restore
fertility using these cells, Orwig and his team biopsied the testes of
prepubertal and adult male macaque monkeys and cryopreserved the cells from the
small samples. The monkeys were then treated with chemotherapy agents known to
impair fertility.
A few months after chemotherapy treatment,
the team re-introduced each monkey's own spermatogonial stem cells back in to
his testes using an ultrasound-guided technique. Sperm production was
established from transplanted cells in nine out of 12 adult animals and three
out of five prepubertal animals after they reached maturity. In another test,
spermatogonial stem cells from other unrelated monkeys were transplanted into
infertile animals, which created sperm with the DNA fingerprint of the donor to
allow easy tracking of their origin. In lab tests, sperm from transplant
recipients successfully fertilized 81 eggs, leading to embryos that developed
to the morula and blastocyst stages, which are the stages that normally precede
implantion in the mother's uterus. Donor parentage was confirmed in seven of
the embryos.
"This study demonstrates that
spermatogonial stem cells from higher primates can be frozen and thawed without
losing their activity, and that they can be transplanted to produce functional
sperm that are able to fertilize eggs and give rise to early embryos,"
Orwig says.
The findings are encouraging because several
centers in the U.S. and abroad already are banking testicular tissue for boys
in anticipation that new stem cell-based therapies will be available in the
future to help them achieve pregnancy and have their own biological children.
"These patients and their families are
the pioneers that inspire our research and help drive the development of new
medical breakthroughs," Orwig says. He directs the Fertility Preservation
Program in Pittsburgh, a unique collaboration between Magee-Womens Research
Institute, Magee-Womens Hospital of UPMC, Children's Hospital of Pittsburgh of
UPMC, and the Univ. of Pittsburgh Cancer Institute that offers education and
treatment options for children as well as adult men and women who are at risk
of becoming infertile due to medical problems including cancer.
"Many questions remain to be
answered," Orwig notes. "Should we re-introduce the spermatogonial
cells as soon as treatment is over, or wait until the patient is considered
cured of his disease, or when he is ready to start a family? How do we
eliminate the risk of cancer recurrence if we give back untreated cells that
might include cancer cells? These are issues we still must work through, but this
study does show us the concept is feasible."
Univ. of Pittsburgh School of
Medicine
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