Xenograft model of heterotopic transplantation of human ovarian cortical tissue and its clinical relevance.
Xenograft model of heterotopic transplantation of human ovarian cortical tissue and its clinical relevance.
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DOI：
10.1530/rep-22-0114
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发表时间：
2023-01-01
期刊：
影响因子：
3.8
通讯作者：
James, Daylon
中科院分区：
文献类型：
--
作者：
Man, Limor;Lustgarten Guahmich, Nicole;Kallinos, Eleni;Park, Laura;Bodine, Richard;Zaninovic, Nikica;Schattman, Glenn;Rosenwaks, Zev;James, Daylon
人卵巢皮质组织的异种移植物提供了一种易于处理的异位自体移植模型，用于接受消融性化疗/放疗的患者的生育力保护。本研究描述了数百个异种移植物的行为，以建立一个框架，卵巢皮质的临床功能后，在短期和长期的时间间隔。使用冷冻保存的卵巢皮质碎片的自体移植已经实现了200多例活产，但挑战仍有待解决。移植组织的缺血破坏了生存能力和寿命，通常需要移植多个皮质块;移植物内的募集动力学以及冷冻保存时尺寸和患者年龄等参数的影响尚未明确。在这里，我们描述了一系列实验的结果，在这些实验中，我们异种移植了来自28名女孩和妇女（年龄范围为32孕周至46岁，中位数为24.3 ± 4.6）的冷冻/解冻的人卵巢组织（n = 440）。异种移植物在广泛的时间间隔（移植后1-52周）内恢复，并进行组织学检查以量化卵泡密度和分布。异种移植皮质骨碎片中有腔卵泡的数量与卵泡总数呈正相关，并随患者年龄的增加而显著减少。在异种移植物中，卵泡分布在焦点簇中，类似于天然卵巢，但存在领先的窦卵泡与周围卵泡的增殖增加相一致。这些结果强调了移植具有高密度卵泡的卵巢组织的重要性，并阐明了领先的有腔卵泡对早期相邻卵泡的潜在旁分泌影响。这一解释卵泡生长/动员动力学的时间框架可能有助于设定预期和指导临床自体移植的参数。
Xenografts of human ovarian cortical tissue provide a tractable model of heterotopic autotransplantation that is used for fertility preservation in patients undergoing ablative chemo/radiotherapy. This study describes the behavior of hundreds of xenografts to establish a framework for the clinical function of ovarian cortex following autotransplantation over short- and long-term intervals. More than 200 live births have been achieved using autotransplantation of cryopreserved ovarian cortical fragments, yet challenges remain to be addressed. Ischemia of grafted tissue undermines viability and longevity, typically requiring transplantation of multiple cortical pieces; and the dynamics of recruitment within a graft and the influence of parameters like size and patient age at the time of cryopreservation are not well-defined. Here, we describe results from a series of experiments in which we xenografted frozen/thawed human ovarian tissue (n = 440) from 28 girls and women (age range 32 weeks gestational age to 46 years, median 24.3 ± 4.6). Xenografts were recovered across a broad range of intervals (1–52 weeks post-transplantation) and examined histologically to quantify follicle density and distribution. The number of antral follicles in xenografted cortical fragments correlated positively with the total follicle number and was significantly reduced with increased patient age. Within xenografts, follicles were distributed in focal clusters, similar to the native ovary, but the presence of a leading antral follicle coincided with increased proliferation of surrounding follicles. These results underscore the importance of transplanting ovarian tissue with a high density of follicles and elucidate a potential paracrine influence of leading antral follicles on neighboring follicles of earlier stages. This temporal framework for interpreting the kinetics of follicle growth/mobilization may be useful in setting expectations and guiding the parameters of clinical autotransplantation.
DOI：
10.1016/j.xfss.2021.07.002
发表时间：
2021-08
期刊：
F&S science
影响因子：
--
作者：
Man, Limor;Lustgarten Guahmich, Nicole;Kallinos, Eleni;Park, Laura;Caiazza, Barbara;Khan, Monica;Liu, Zong-Ying;Patel, Ritaben;Torres, Carmen;Lekovich, Jovana;Zhong, Liangwen;Bodine, Richard;Wen, Duancheng;Zaninovic, Nikica;Schattman, Glenn;Rosenwaks, Zev;James, Daylon
通讯作者：
James, Daylon