Manavella D D, Herraiz Sonia, Soares M, Buigues A, Pellicer A, Donnez J, Díaz-García C, Dolmans M M
Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Mounier 52, bte. B1.52.02, 1200, Brussels, Belgium.
Neolife-Medicina y Cirugía Reproductiva, Brasilia 760, 1434, Asunción, Paraguay.
J Assist Reprod Genet. 2021 Jun;38(6):1589-1600. doi: 10.1007/s10815-021-02169-2. Epub 2021 Mar 31.
Cryopreserved ovarian tissue transplant restores ovarian function in young cancer patients after gonadotoxic treatment. However, leukemia is associated with increased risk of malignant cell transmission. We aimed to assess the tumor-inducing potential of two different leukemic cell lines when xenografted to immunodeficient mice.
Fifty-four female immunodeficient mice were grafted with either 100, 200, 500, 1000, and 10,000 chronic myeloid leukemia in blast crisis (BV-173) cells or relapsed acute lymphoblastic leukemia (RCH-ACV) cells, embedded inside a fibrin scaffold along with 50,000 human ovarian stromal cells. Two mice per cell line received the fibrin matrix without leukemic cells as negative controls. Clinical signs of disease were monitored for 20 weeks. Grafts, liver tissue, and masses were collected for macroscopic analysis and gene expression of BCR-ABL1 and E2A-PBX fusion transcripts present in BV-173 and RCH-ACV respectively.
BV-173 cells: Mice grafted with 100, 200, or 500 cells showed no sign of disease after and were negative for BCR-ABL1 expression. Three of the 5 animals grafted with 1000 cells and all mice with 10,000 cells developed disease and showed BCR-ABL1-positive expression. RCH-ACV cells: Two out of 4 mice grafted with 100 cells developed disease and were E2A-PBX1-positive. All the animals grafted with higher cell doses showed signs of disease and all but one were E2A-PBX1-positive.
The present work proves that the disease-inducing potential of BV-173 and RCH-ACV leukemic cells xenografted to SCID mouse peritoneum differs between cell lines, depending on cell number, type, status, and cytogenetic disease profile when ovarian tissue is harvested.
冷冻保存的卵巢组织移植可恢复接受性腺毒性治疗的年轻癌症患者的卵巢功能。然而,白血病与恶性细胞传播风险增加有关。我们旨在评估两种不同白血病细胞系异种移植到免疫缺陷小鼠后诱导肿瘤的潜力。
将54只雌性免疫缺陷小鼠分别移植100、200、500、1000和10000个处于急变期的慢性髓性白血病(BV - 173)细胞或复发性急性淋巴细胞白血病(RCH - ACV)细胞,这些细胞与50000个人类卵巢基质细胞一起包埋在纤维蛋白支架内。每个细胞系有两只小鼠接受不含白血病细胞的纤维蛋白基质作为阴性对照。对疾病的临床症状进行20周监测。收集移植物、肝脏组织和肿块进行宏观分析,并检测分别存在于BV - 173和RCH - ACV中的BCR - ABL1和E2A - PBX融合转录本的基因表达。
BV - 173细胞:移植100、200或500个细胞的小鼠在移植后未出现疾病迹象,且BCR - ABL1表达为阴性。移植1000个细胞的5只动物中有3只以及移植10000个细胞的所有小鼠都发生了疾病,并显示BCR - ABL1阳性表达。RCH - ACV细胞:移植100个细胞的4只小鼠中有2只发生了疾病,且E2A - PBX1呈阳性。移植更高细胞剂量的所有动物均出现疾病迹象,除一只外其余均为E2A - PBX1阳性。
目前的研究证明,异种移植到SCID小鼠腹膜的BV - 173和RCH - ACV白血病细胞诱导疾病的潜力因细胞系而异,这取决于收获卵巢组织时的细胞数量、类型、状态和细胞遗传学疾病谱。