Hou Mi, Andersson Margareta, Eksborg Staffan, Söder Olle, Jahnukainen Kirsi
Department of Women and Child Health, Astrid Lindgren Children's Hospital, Pediatric Endocrinology Unit, Q2:08, Karolinska Institute and University Hospital, SE-171 76 Stockholm, Sweden.
Hum Reprod. 2007 Jul;22(7):1899-906. doi: 10.1093/humrep/dem085. Epub 2007 Apr 23.
Xeno-grafting of testicular tissue may allow viable gamete maturation. This would be beneficial for prepubertal cancer patients in that it may allow restoration of fertility without the risk of a cancer relapse. However it is unknown whether cancer cells in the testicular graft can transmit the malignancy into the host animal and also if gametes can be retrieved from testicular grafts that are contaminated with malignant cells.
Rat T-cell leukemia was employed as the source of leukemic lymphoblasts and testicular tissue. This was injected i.p. (lymphoblasts) or grafted s.c. (fresh or cryopreserved testicular tissue) into the back skin of intact nude mice. To simulate clinical autografting, testicular tissue was also transplanted into healthy piebald variegated (PVG) rats.
50-70% of the mice, receiving 200 or 6000 leukemic lymphoblasts, developed terminal leukemia. All mice, grafted with either fresh or cryopreserved testicular tissue from leukemic donor, developed generalized leukemia and/or local tumors. All syngenic PVG rats, treated in the same manner, died of generalized leukemia. In all of the retrieved leukemic grafts, rat spermatogenesis was destroyed and only leukemic infiltration was detected.
Grafting testicular tissue contaminated with leukemic cells led to tumor growth at the injection site without potential to differentiate germline stem cells into gametes. Xenografting could provide a novel functional strategy for simultaneous detection of malignant cell contamination and spermatogonial potential in testicular xenografts collected for fertility preservation.
睾丸组织的异种移植可能使有活力的配子成熟。这对青春期前癌症患者有益,因为它可能恢复生育能力而无癌症复发风险。然而,尚不清楚睾丸移植物中的癌细胞是否会将恶性肿瘤传播给宿主动物,以及能否从被恶性细胞污染的睾丸移植物中获取配子。
将大鼠T细胞白血病作为白血病淋巴母细胞和睾丸组织的来源。将其经腹腔注射(淋巴母细胞)或皮下移植(新鲜或冷冻保存的睾丸组织)到完整裸鼠的背部皮肤。为模拟临床自体移植,睾丸组织也被移植到健康的花斑杂色(PVG)大鼠体内。
接受200或6000个白血病淋巴母细胞的小鼠中,50 - 70%发展为终末期白血病。所有移植了来自白血病供体的新鲜或冷冻保存睾丸组织的小鼠,均发展为全身性白血病和/或局部肿瘤。所有以相同方式处理的同基因PVG大鼠均死于全身性白血病。在所有回收的白血病移植物中,大鼠精子发生被破坏,仅检测到白血病浸润。
移植被白血病细胞污染的睾丸组织会导致注射部位肿瘤生长,且无法将生殖系干细胞分化为配子。异种移植可为同时检测用于生育力保存所采集的睾丸异种移植物中的恶性细胞污染和精原细胞潜能提供一种新的功能策略。