title: Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia.
abstract: 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.
authors.affiliation: 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.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohta
authors.forename: Akira
authors.initials: A
authors.lastname: Tsujimura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takao
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyagawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Takada
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Matsumiya
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Wakayama
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuyama
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents