Fujita Kazutoshi, Tsujimura Akira
Department of Urology Osaka General Medical Center 3-1-56 Bandai-hiagashi, Sumiyoshi 558-8558 Osaka Japan.
Department of Urology Osaka University Graduate School of Medicine 2-2 Yamadaoka 565-0871 Suita Osaka Japan.
Reprod Med Biol. 2010 Aug 7;9(4):179-184. doi: 10.1007/s12522-010-0061-6. eCollection 2010 Dec.
Childhood cancer is a curable disease due to the development of chemo- and radiation therapies, but long-term survivors suffer late side-effects including infertility. Cytotoxic agents and radiation impair spermatogenesis and cause oligospermia or azoospermia as well as genetic damage in sperm. To date, the only established option to preserve fertility is cryopreservation of sperm before treatment and artificial reproduction techniques, if men with cancer can ejaculate, but only a quarter of men have banked sperm. Lack of information is the most common reason for failing to bank sperm. However, prepubertal patients who have only spermatogonia and spermatocytes in their testes do not benefit from cryopreservation of their sperm and assisted reproductive techniques. Thus, the only available option is to harvest testicular tissues before treatment for cryopreservation, from which immature germ cells can somehow be maturated. Autotransplantation of germ cells into the testis holds promise for fertility restoration, but contamination by malignant cells may induce relapse. Fluorescence-activated cell sorting (FACS) with two surface markers could exclude contaminated leukemic cells from murine germ cells, and transplantation of sorted germ cells successfully restored fertility without transmission of leukemia. Human germ cells could be also isolated from human leukemia and lymphoma cell lines by FACS using surface markers. Before autotransplantation can be applied clinically, some issues, including the risk of contamination by malignant cells and in vitro propagation of spermatogonial stem cells, should be resolved.
由于化疗和放疗技术的发展，儿童癌症已成为一种可治愈的疾病，但长期存活者会遭受包括不育在内的晚期副作用。细胞毒性药物和辐射会损害精子发生，导致少精子症或无精子症，以及精子的基因损伤。迄今为止，如果癌症男性能够射精，保存生育能力的唯一既定选择是在治疗前冷冻精子以及采用人工生殖技术，但只有四分之一的男性储存了精子。信息缺乏是未能储存精子的最常见原因。然而，睾丸中只有精原细胞和精母细胞的青春期前患者无法从精子冷冻保存和辅助生殖技术中获益。因此，唯一可行的选择是在治疗前采集睾丸组织进行冷冻保存，从中的未成熟生殖细胞可以以某种方式成熟。将生殖细胞自体移植到睾丸有望恢复生育能力，但恶性细胞的污染可能会导致复发。利用两种表面标志物进行荧光激活细胞分选（FACS）可以从小鼠生殖细胞中排除受污染的白血病细胞，分选后的生殖细胞移植成功恢复了生育能力，且未传播白血病。也可以使用表面标志物通过FACS从人白血病和淋巴瘤细胞系中分离出人生殖细胞。在自体移植能够应用于临床之前，一些问题，包括恶性细胞污染的风险和精原干细胞的体外增殖，需要得到解决。
