Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia

While more than 70% of patients survive childhood leukemia, curative chemotherapy can often irreversibly impair the formation of spermatozoa, causing infertility in males.

Currently, the only established clinical option for the preservation of fertility in leukemia patients is to bank sperm before treatment commences.

However, as mature germ cells do not develop until the onset of puberty, children are unable to later benefit from such assisted reproductive techniques.

Although the transplantation of one's own germ cells after chemotherapy holds promise for restoring fertility, a major hurdle has been the risk of contamination by leukemic cells, which may induce relapse.

Now, in a study appearing online on June 16 in advance of print publication in the July 1 issue of the Journal of Clinical Investigation, Akira Tsujimura and colleagues from Osaka University describe a way in which healthy germ cells, including spermatogonial stem cells, can be distinguished and completely separated from leukemic cells in mice, and then harvested and preserved.

These cells were then transplanted into the gonads of healthy recipient mice previously exposed to chemotherapeutic agents.

The transplanted germ cells successfully colonized and were able to produce healthy progeny.

The successful birth of offspring of recipient mice, without the transmission of leukemia to the recipient, suggests the potential of autotransplantation of carefully sorted germ cells in order to treat the infertility that arises as a result of anticancer treatment for childhood leukemia.

A number of issues surrounding the harvest of such material from prepubertal children with leukemia, that could be safely stored and retransplanted into chemotherapy-damaged testes, have not yet been solved.

These include: (i) the harvest of sufficient numbers of healthy germ cells, without significant tissue loss; (ii) careful isolation of germ cells, including stem cells, from the population of malignant cells to avoid relapse; and (iii) ensuring that isolated germ cells are able to undergo normal spermatogenesis. However, this overall approach may hold great potential for the treatment of infertility following recovery from childhood leukemia.

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