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利用脂肪组织来源的干细胞提高卵巢组织移植存活率的转化研究。

Translational research aiming to improve survival of ovarian tissue transplants using adipose tissue-derived stem cells.

机构信息

Research Center in Gynecology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium.

Gynecology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

出版信息

Acta Obstet Gynecol Scand. 2019 May;98(5):665-671. doi: 10.1111/aogs.13610. Epub 2019 Apr 13.

Abstract

There is now sufficient evidence to support the feasibility and efficacy of ovarian tissue (OT) cryopreservation and transplantation for both fertility preservation and restoration purposes. However, there are still issues to address regarding the grafting procedure itself, since transplanted tissue suffers massive follicle loss in the early post-grafting period. To improve follicle survival after transplantation, our group recently developed a two-step transplantation technique for OT transplantation in a xenografting model using adipose tissue-derived stem cells (ASCs). The aim of this narrative review is to describe and discuss the previously reported findings. ASCs were initially characterized by flow cytometry as positive for CD29, CD44, CD73, CD90, CD105 and CD166 (>95%) and negative for CD34, CD14, CD31, CD45 and Lin1. ASCs were used in a model of xenotransplantation, were they were embedded in a fibrin scaffold and transplanted to the peritoneum of immunodeficient mice. The goal of the first step was to increase levels of partial pressure of oxygen (pO ) and revascularization in the peritoneal transplantation site for further OT transplantation. As ASCs showed the ability to differentiate into endothelial-like cells and vessels in our model, OT transplantation was then performed with ASC grafts in a controlled experiment. At 7 days post-transplantation, the ASC group showed: (1) significantly higher pO levels; (2) significantly greater human and murine CD34-positive endothelial areas; (3) significantly higher primordial follicle survival rates; (4) and significantly lower numbers of apoptotic follicles compared with the control group. Our research model demonstrates that by adding ASCs to a fibrin scaffold before OT transplantation, faster and better graft reoxygenation and revascularization may be obtained, resulting in increased follicle survival and reduced follicle apoptosis.

摘要

现在有足够的证据支持卵巢组织 (OT) 冷冻保存和移植用于生育力保存和恢复的可行性和疗效。然而,关于移植程序本身仍存在一些问题,因为移植组织在移植后的早期会遭受大量卵泡损失。为了提高移植后的卵泡存活率,我们小组最近在使用脂肪组织衍生干细胞 (ASCs) 的异种移植模型中开发了一种 OT 两步移植技术。本叙述性综述的目的是描述和讨论以前的报告结果。ASCs 最初通过流式细胞术鉴定为 CD29、CD44、CD73、CD90、CD105 和 CD166(>95%)阳性,CD34、CD14、CD31、CD45 和 Lin1 阴性。ASCs 用于异种移植模型中,嵌入纤维蛋白支架并移植到免疫缺陷小鼠的腹膜中。第一步的目标是增加腹膜移植部位的氧分压 (pO ) 和再血管化水平,以便进一步进行 OT 移植。由于 ASCs 在我们的模型中显示出分化为内皮样细胞和血管的能力,因此在对照实验中进行了带有 ASC 移植物的 OT 移植。移植后 7 天,ASC 组表现出:(1) pO 水平显著升高;(2) 人源和鼠源 CD34 阳性内皮区域显著增大;(3) 原始卵泡存活率显著升高;(4) 与对照组相比,凋亡卵泡数量显著减少。我们的研究模型表明,通过在 OT 移植前将 ASC 添加到纤维蛋白支架中,可以获得更快、更好的移植物再氧合和再血管化,从而增加卵泡存活率并减少卵泡凋亡。

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