Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia.
More than 70% of patients survive childhood leukemia, but chemotherapy and radiation therapy cause irreversible impairment of spermatogenesis. Although autotransplantation of germ cells holds promise for restoring fertility, contamination by leukemic cells may induce relapse. In this study, we isolated germ cells from leukemic mice by FACS sorting. The cell population in the high forward-scatter and low side-scatter regions of dissociated testicular cells from leukemic mice were analyzed by staining for MHC class I heavy chain (H-2K/H-2D) and for CD45. Cells that did not stain positively for H-2K/H-2D and CD45 were sorted as the germ cell-enriched fraction. The sorted germ cell-enriched fractions were transplanted into the testes of recipient mice exposed to alkylating agents. Transplanted germ cells colonized, and recipient mice survived. Normal progeny were produced by intracytoplasmic injection of sperm obtained from recipient testes. When unsorted germ cells from leukemic mice were transplanted into recipient testes, all recipient mice developed leukemia. The successful birth of offspring from recipient mice without transmission of leukemia to the recipients indicates the potential of autotransplantation of germ cells sorted by FACS to treat infertility secondary to anticancer treatment for childhood leukemia.
Fujita
Kazutoshi
K
Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan. Laboratory for Genomic Reprogramming, Center for Developmental Biology, Institute of Physical and Chemical Research (RIKEN), Kobe, Japan.
Ohta
Hiroshi
H
Tsujimura
Akira
A
Takao
Tetsuya
T
Miyagawa
Yasushi
Y
Takada
Shingo
S
Matsumiya
Kiyomi
K
Wakayama
Teruhiko
T
Okuyama
Akihiko
A
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D002469:Cell Separation; D005260:Female; D005298:Fertility; D005434:Flow Cytometry; D006801:Humans; D007248:Infertility, Male / Q000209:etiology / Q000628:therapy; D007942:Leukemia, Experimental / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic; D013093:Spermatogonia / Q000637:transplantation*; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D014185:Transplantation, Isogeneic
D000970:Antineoplastic Agents