Reconstruction of the ovary microenvironment utilizing macroporous scaffold with affinity-bound growth factors
Reconstruction of the ovary microenvironment utilizing macroporous scaffold with affinity-bound growth factors
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DOI：
10.1016/j.biomaterials.2019.03.013
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发表时间：
2019-06-01
期刊：
影响因子：
14
通讯作者：
Cohen, Smadar
中科院分区：
文献类型：
--
作者：
Felder, Shani;Masasa, Hila;Cohen, Smadar
实施卵巢组织工程使卵巢中最丰富的卵泡群--原始卵泡成熟，对女性生育力的保护具有巨大的潜力。在这里，我们评估了大孔藻酸盐支架与亲和结合的骨形态发生蛋白-4（BMP-4）是否可以模拟卵巢微环境，并支持与支持卵巢细胞接种的原始卵泡的培养和生长。猪原始卵泡在藻酸盐支架中21天内发育至腔前阶段。亲和力结合的BMP-4显著促进卵泡成熟，如通过与当BMP-4添加到无亲和力结合的培养物中时相比，这些培养物中发育卵泡的数量增加5倍和雌二醇分泌增强所证明的。培养21天后，与所有其他支架组相比，当BMP-4亲和结合时，与卵泡发育相关的GDF-9/AMH基因表达的增加具有统计学显著性。当在体内开发时，在补充有额外的血管生成因子的卵泡装置的异种移植后，卵泡达到窦大小并分泌激素，其水平导致卵巢切除的严重联合免疫缺陷（SCID）小鼠的卵巢功能恢复。总之，我们的研究结果提供了第一次肯定的适用性大孔藻酸盐支架作为一个合适的平台，促进卵泡成熟的体外和体内，并奠定了基础，有利地利用亲和结合的生长因子的介绍，培养卵泡。
Implementing ovarian tissue engineering for the maturation of primordial follicles, the most abundant follicle population in the ovary, holds great potential for women fertility preservation. Here, we evaluated whether macroporous alginate scaffolds with affinity-bound bone morphogenetic protein-4 (BMP-4) could mimic the ovary microenvironment and support the culture and growth of primordial follicles seeded with supporting ovarian cells. Porcine primordial follicles developed in the alginate scaffolds up to the pre-antral stage within 21 days. Affinity-bound BMP-4 significantly contributed to follicular maturation, as evident by the 5-fold increase in the number of developing follicles and enhanced estradiol secretion in these cultures compared to when BMP-4 was added to cultures with no affinity binding. After 21 days in culture, an increase in GDF-9/AMH gene expression, which is correlated with follicular development, was statistically significant when BMP-4 was affinity bound, compared to all other scaffold groups. When developed in-vivo, after xeno-transplantation of the follicle devices supplemented with additional angiogenic factors, the follicles reached antral size and secreted hormones at levels leading to restoration of ovarian function in ovariectomized severe combined immunodeficiency (SCID) mice. Altogether, our results provide first affirmation for the applicability of macroporous alginate scaffolds as a suitable platform for promoting follicle maturation in-vitro and in-vivo, and lay the foundations for the advantageous use of affinity binding presentation of growth factors to cultured follicles.