Engineered multilayer ovarian tissue that secretes sex steroids and peptide hormones in response to gonadotropins.

Engineered multilayer ovarian tissue that secretes sex steroids and peptide hormones in response to gonadotropins.
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响应促性腺激素的工程多层卵巢组织,分泌性类固醇和肽激素。

DOI:
10.1016/j.biomaterials.2012.11.059
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发表时间:
2013-03
期刊:
影响因子:
14
通讯作者:
Opara, Emmanuel C.
Opara, Emmanuel C.
中科院分区:
工程技术1区
文献类型:
--
作者:
Sittadjody, Sivanandane;Saul, Justin M.;Joo, Sunyoung;Yoo, James J.;Atala, Anthony;Opara, Emmanuel C.

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尽管激素替代疗法是卵巢功能丧失的一种选择,但通过药理学手段输送激素会导致各种临床并发症。本研究旨在通过使用封装技术制造的功能性结构来递送性类固醇。从 21 日龄大鼠卵巢中分离的卵泡膜和颗粒细胞被封装在多层藻酸盐微胶囊中,以重现天然卵泡结构。使用另外两种方案封装的电池作为对照来评估多层结构的重要性。封装细胞的内分泌功能在体外进行为期30天的评估。封装的细胞在长期体外培养过程中表现出持续的活力,封装在多层胶囊中的细胞响应卵泡刺激素 (FSH) 和黄体生成素 (LH),比其他两种封装方案 (p<0.05,n=6) 分泌显着更高且持续浓度的 17 β-雌二醇 (E2)。此外,多层微胶囊中的细胞还在体外分泌激活素和抑制素。相反,当颗粒细胞和卵泡膜细胞在 2-D 培养中培养时,孕酮 (P4) 分泌增加,而 E2 分泌在 30 天期间减少。总之,我们设计了一种多层工程卵巢组织,它能分泌性类固醇和肽激素并对促性腺激素做出反应,从而证明了在体外重现天然卵巢结构的能力。
Although hormone replacement therapy is an option for the loss of ovarian function, hormone delivery through pharmacological means results in various clinical complications. The present study was designed to deliver sex steroids by a functional construct fabricated using encapsulation techniques. Theca and granulosa cells isolated from ovaries of 21-day old rats were encapsulated in multilayer alginate microcapsules to recapitulate the native follicular structure. Cells encapsulated in two other schemes were used as controls to assess the importance of the multilayer structure. The endocrine functions of the encapsulated cells were assessed in vitro for a period of 30 days. Encapsulated cells showed sustained viability during long-term in vitro culture with those encapsulated in multilayer capsules secreting significantly higher and sustained concentrations of 17 β-estradiol (E2) than the two other encapsulation schemes (p<0.05, n=6) in response to follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In addition, cells in the multilayer microcapsules also secreted activin and inhibin in vitro. In contrast, when granulosa and theca cells were cultured in 2-D culture, progesterone (P4) secretion increased while E2 secretion decreased over a 30-day period. In summary, we have designed a multilayer engineered ovarian tissue that secretes sex steroids and peptide hormones and responds to gonadotropins, thus demonstrating the ability to recapitulate native ovarian structure ex vivo.
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发表时间: 2010-11
影响因子: 4.9
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