Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia
Transplantation of spermatogonial stem cells isolated from leukemic mice restores fertility without inducing leukemia
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DOI：
10.1172/jci24189
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发表时间：
2005-07-01
影响因子：
15.9
通讯作者：
Okuyama, A
中科院分区：
文献类型：
--
作者：
Fujita, K;Ohta, H;Okuyama, A
超过70%的儿童白血病患者存活，但化疗和放疗导致精子发生不可逆转的损害。虽然生殖细胞自体移植有望恢复生育能力，但被白血病细胞污染可能导致复发。在这项研究中，我们用FACS分选法分离白血病小鼠的生殖细胞。通过MHC I类重链(H-2K（b/) H-2D(b)）和CD45染色，分析白血病小鼠睾丸解离细胞高正向散射区和低侧散射区细胞群。对H-2K(b)/H-2D(b)和CD45染色不阳性的细胞分选为生殖细胞富集部分。将分选的生殖细胞富集组分移植到接触烷基化剂的受体小鼠睾丸中。移植的生殖细胞定植，受体小鼠存活。从受体睾丸中获得的精子通过胞浆内注射产生正常后代。当将白血病小鼠未分类的生殖细胞移植到受体睾丸时，所有受体小鼠都患上了白血病。受体小鼠的后代成功出生而没有将白血病传播给受体，这表明FACS分类的生殖细胞自身移植治疗儿童白血病抗癌治疗继发性不孕症的潜力。
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(b/) H-2D(b)) and for CD45. Cells that did not stain positively for H-2K(b)/H-2D(b) 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.