Researchers from the University and two other institutions have immortalized a stem cell line from the testis and used it to reproduce in culture several of the stages of sperm cell development, according to a study published last month on the Science Express Web site, part of the journal Science.
The new stem cell line is not capable of transforming into different cell types. Researchers will use it strictly to study sperm development and possibly create new genetic therapies.
Curing human embryos of genetic disease with germ cell gene therapy is now an even greater possibility. A clear picture of the development and function of sperm cells is paramount for the development of such treatments.
Sperm undergo a complex developmental process, which includes dramatic changes in form such as tail growth.
These changes prepare the sperm for their reproductive purpose outside the body.
Understanding the molecular steps that transform cells into mature sperm will help medical experts better understand illnesses such as infertility and testicular cancer. The results also might lead to new germ cell gene therapies.
In this kind of gene therapy, the genetic makeup of sex cells, eggs and sperm, is altered. Since these changes are made to cells responsible for reproduction, the alterations are passed on to all future offspring.
The sperm cell line developed by the team of researchers replicates and grows in a tissue culture dish, providing a model for scientists to study sperm development, referred to as spermatogenesis.
Previous efforts to create a cell line capable of replicating and growing outside the body have been unsuccessful, impeding research in the field.
"It's a barrier to research progress that has been recognized for at least 15 years," said John Herr, University cell biology professor and co-investigator of the study. "The understanding of gene regulation during spermatogenesis has been delayed."
For a field of research that once was hindered by the absence of a good model for sperm development, the new stem cell line is a valuable tool for understanding the intricate progression of spermatogenesis, and provides opportunities to transplant genetically-altered cells into host animals.
It also might lead to new strategies for germ cell gene therapy, Herr said.
In contrast to conventional therapies that treat genetic diseases after the patient already has been diagnosed, gene therapy is designed to intervene at the genetic level by replacing the erroneous DNA with a correct version. Thus, successful gene therapy cures the disease before it has a chance to appear.
There are two types of gene therapy, somatic and germ line. Somatic gene therapy is directed at non-reproductive cells such as liver or kidney cells. Alternatively, germ line gene therapy focuses on altering the genetic material in reproductive cells, such as sperm.
Changes made in a somatic cell's genetic composition cease to exist after the individual dies and cannot be passed on to offspring. This is the key difference between somatic cell and germ cell gene therapy.
By making genetic changes in sperm, germ cell gene therapy not only changes the genes in every cell of the patient, but also alters the genetic material passed down to future offspring.
"The potential implications of this cell line for germ cell gene therapy are far-reaching, although this technology will require many more years of study before it is ready for humans," said Martin Dym, chair of cell biology at Georgetown University Medical Center and co-author of the report.
Dym also said in a press release that scientists might one day be able to remove defective genes in sperm stem cells that cause diseases such as cystic fibrosis or hemophilia and transplant these corrected stem cells back into the testis. This would prevent future offspring from contracting that particular disease.
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