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使用免疫调节因子着床前因子(PIF)作为单一疗法的同种异体卵巢移植恢复了东非狒狒的卵巢功能。

Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon.

作者信息

Feichtinger Michael, Barnea Eytan R, Nyachieo Atunga, Brännström Mats, Kim S Samuel

机构信息

Department of Obstetrics and Gynecology, Division of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria.

Wunschbaby Institut Feichtinger, Vienna, Austria.

出版信息

J Assist Reprod Genet. 2018 Jan;35(1):81-89. doi: 10.1007/s10815-017-1051-y. Epub 2017 Nov 11.

DOI:10.1007/s10815-017-1051-y
PMID:29128910
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5758471/
Abstract

PURPOSE

Allogeneic ovarian transplantation may be an alternative in the future to oocyte donation in women with premature ovarian failure. The objectives of this study were to (a) evaluate allotransplantation feasibility for restoration of ovarian function and (b) assess efficacy of synthetic preimplantation factor (PIF) monotherapy as sole immune-acceptance regimen.

METHODS

This is an experimental animal study using non-human primates (Papio anubis). Allogeneic orthotopic ovarian tissue transplantation was performed in two female olive baboons. PIF was administered as a monotherapy to prevent immune rejection and achieve transplant maintenance and function. Subjects underwent bilateral oophorectomy followed by cross-transplantation of prepared ovarian cortex. Postoperatively, subjects were monitored for clinical and biochemical signs of graft rejection and return of function. Weekly blood samples were obtained to monitor graft acceptance and endocrine function restoration.

RESULTS

Postoperatively, there were no clinical signs of rejection. Laboratory parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine) did not indicate organ rejection at any stage of the experiment. Initially, significant loss of follicles was noticed after grafting and serum follicle-stimulating hormone (FSH) and E2 levels were consistent with ovarian failure. Seven months after transplantation, one animal exhibited recurrence of ovarian endocrine function (perineal swelling, E2 rise, FSH decrease, and return of menstruation).

CONCLUSIONS

Organ rejection after allogeneic ovarian transplantation was prevented using PIF as monotherapy for the first time and no side effects were recorded. The study suggests the clinical feasibility of ovarian allotransplantation to obtain ovarian function.

摘要

目的

同种异体卵巢移植未来可能成为卵巢早衰女性卵母细胞捐赠的一种替代方法。本研究的目的是:(a)评估同种异体移植恢复卵巢功能的可行性;(b)评估合成植入前因子(PIF)单一疗法作为唯一免疫接受方案的疗效。

方法

这是一项使用非人灵长类动物(埃及狒狒)的实验性动物研究。在两只雌性东非狒狒身上进行了同种异体原位卵巢组织移植。给予PIF单一疗法以防止免疫排斥并实现移植维持和功能。研究对象接受双侧卵巢切除术,然后进行制备好的卵巢皮质交叉移植。术后,监测研究对象是否出现移植物排斥和功能恢复的临床及生化迹象。每周采集血样以监测移植物接受情况和内分泌功能恢复情况。

结果

术后,没有排斥的临床迹象。实验室参数(丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血尿素氮(BUN)、肌酐)在实验的任何阶段均未表明器官排斥。最初,移植后发现卵泡显著丢失,血清促卵泡生成素(FSH)和E2水平与卵巢功能衰竭一致。移植七个月后,一只动物出现卵巢内分泌功能复发(会阴部肿胀、E2升高、FSH降低和月经恢复)。

结论

首次使用PIF单一疗法预防了同种异体卵巢移植后的器官排斥,且未记录到副作用。该研究表明卵巢同种异体移植以获得卵巢功能具有临床可行性。

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本文引用的文献

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Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response.合成植入前因子(PIF)通过调节脂多糖诱导的炎症反应来防止胎儿丢失。
PLoS One. 2017 Jul 12;12(7):e0180642. doi: 10.1371/journal.pone.0180642. eCollection 2017.
2
PIF* promotes brain re-myelination locally while regulating systemic inflammation- clinically relevant multiple sclerosis M.smegmatis model.PIF* 在调节系统性炎症的同时,在局部促进脑髓鞘再生——临床相关的耻垢分枝杆菌多发性硬化模型。
Oncotarget. 2017 Mar 28;8(13):21834-21851. doi: 10.18632/oncotarget.15662.
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PreImplantation factor (PIF) therapy provides comprehensive protection against radiation induced pathologies.植入前因子(PIF)疗法可为辐射诱发的病症提供全面保护。
Oncotarget. 2016 Sep 13;7(37):58975-58994. doi: 10.18632/oncotarget.10635.
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PreImplantation factor (PIF*) regulates systemic immunity and targets protective regulatory and cytoskeleton proteins.着床前因子(PIF*)调节全身免疫,并作用于保护性调节蛋白和细胞骨架蛋白。
Immunobiology. 2016 Jul;221(7):778-93. doi: 10.1016/j.imbio.2016.02.004. Epub 2016 Feb 23.
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PreImplantation factor prevents atherosclerosis via its immunomodulatory effects without affecting serum lipids.着床前因子通过其免疫调节作用预防动脉粥样硬化,而不影响血脂。
Thromb Haemost. 2016 May 2;115(5):1010-24. doi: 10.1160/TH15-08-0640. Epub 2016 Feb 4.
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