FRIDAY, June 17, 2005 (HealthDay News) -- Chemotherapy and radiation offer millions of adolescent children with leukemia a good shot at a cure, but the lifesaving treatments can come at a price, often rendering the young survivors sterile for life.
To try to circumvent this side effect, a team of Japanese researchers turned to mice with leukemia -- successfully isolating, extracting and freezing healthy sperm stem cells before treatment and then reinserting the cells once the mice were found to be leukemia-free.
The procedure preserved the ability of the mice to produce mature and healthy sperm after treatment, without risking the return of the cancer, the researchers report in the July 1 issue of the Journal of Clinical Investigation.
"We performed germ cell transplantation, and showed successful development of germ cells to mature sperm in testes impaired by chemotherapy, and recipient mice survived," said study author Dr. Kazutoshi Fujita, of the department of urology at Osaka University Graduate School of Medicine.
Fujita and his colleagues note that roughly 141 million children are diagnosed with cancer each year worldwide. Among this group, leukemia is the most common diagnosis -- amounting to approximately 30 percent of cancer cases among children under the age of 15.
While 70 percent of children battling leukemia survive, between a quarter and a third of the survivors are rendered infertile by radiation and/or chemotherapy.
The researchers also point out that pre-pubescent boys with leukemia do not have mature sperm that can be ejaculated and frozen for later use -- an option available to adult male patients.
The authors sought to develop a fertility preservation technique that would aid these young patients. They turned to unaffected stem cells present in testicular tissue that could later develop into mature sperm once reintroduced.
Fujita's team focused on 12 mice previously affected by leukemia but cured with chemotherapy. Prior to the chemotherapy treatments, the researchers extracted sperm stem cells from each mouse's testes.
After eradicating the leukemia, the team re-inserted the sperm stem cells back into the mouse's testes, first carefully sorting and identifying these cells as being leukemia-free. An additional 12 cured mice were injected with unsorted sperm stem cells potentially contaminated by leukemic cells.
The researchers found that the 12 mice injected with the sorted sperm stem cells continued to be leukemia-free 300 days after the procedure, while the other 12 mice injected with the unsorted cells went on to develop typical signs of the cancer within 40 days of the procedure.
The sperm stem cell transplant group also went on to produce healthy sperm and healthy offspring. Neither the mice nor their pups displayed signs of leukemia.
While Fujita and his colleagues expressed enthusiasm for their findings, they simultaneously emphasized the need to further hone the technique before testing it on a human population.
They stressed the need to minimize the potential mixing of healthy stem cells with leukemia cells, so as to avoid the possibility of transplanting so much as a single life-threatening cancer cell into an otherwise cured patient. For that reason, researchers are still years away from being able to successfully apply the findings to humans, Fujita explained.
"Technical errors may lead to contamination of donor cells by malignant cells, (so) sensitive methods to detect contamination by a single cell should be developed before clinical application to humans," he cautioned.
Dr. Larry L. Lipshultz, chief of the division of male reproductive medicine in the department of urology at Baylor College of Medicine in Houston, said he is both interested in and familiar with the science behind the study, having conducted similar stem cell removal and reinsertions in his own laboratory work. And he cautioned that formidable obstacles loom over efforts to perfect such fertility treatments for human patients.
"The problem with this whole thing is that you've got to transfer a significant volume of stem cells in order to get a significant number of sperm cells," cautioned Lipshultz. "It's biologically a challenge, because you can't biopsy a lot of tissue from a child. You have to leave him some testicular tissue. So right now, we're not there yet in terms of the number of cells we can transfer back."
Lipshultz said, however, that such problems are not insurmountable. And he added that the Japanese study highlights the potential that stem cell research holds out for improving treatments not just for leukemia patients, but also for patients facing a broad range of medical issues.
More information
For more on stem cells and disease, check out the National Institutes of Health.
