Sorting out fertility for childhood cancer survivors

Fertility in male childhood cancer survivors may be preserved by sorting out spermatogonial stem cells (SSCs) from malignant material prior to the start of treatment. A recent study has shown promise in a mouse model.

As success rates in treating childhood cancers have improved, greater emphasis is being placed on quality of life issues following successful treatment. Many cancer treatments can lead to infertility, but few methods exist to preserve the fertility of children who have not yet entered puberty.

SSCs, which produce sperm cells, are present at the start of puberty. In theory, SSCs could be removed via biopsy prior to the start of treatment and then retransplanted following remission. However, there is a potential risk of reintroducing malignant material during transplantation. This hurdle was overcome by Kyle Orwig and colleagues at the University of Pittsburgh. They characterized the cell surface markers of human spermatogonia in testicular tissue from organ donors.

The research team used fluorescence-assisted cell sorting (FACS) flow cytometry to characterize cell surface antigen expression on human testicular cells and leukemic cells. They found that EpCAM is expressed by human spermatogonia but not by the leukemic cells. Further, HLA-ABC and CD49e were found to be expressed by more than 95% of the leukemic cells but not by the human spermatogonia. Human spermatogonia cells that were contaminated with leukemic cells were sorted by a multiparameter sort. The fraction representing the human spermatogonia cells did not form tumors after they were transplanted into nude mice, which are mice with an inhibited immune system.

The authors concluded that their work with “FACS provides a method to isolate and enrich human spermatogonia and remove malignant contamination by exploiting differences in cell surface antigen expression.” These results suggest that SSC transplantation could be a viable method to preserve fertility in male childhood cancer survivors. The study was reported in Journal of Clinical Investigation (2013; doi:10.1172/JCI65822).

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