Sequestered cell-secreted extracellular matrix proteins improve murine folliculogenesis and oocyte maturation for fertility preservation.
Sequestered cell-secreted extracellular matrix proteins improve murine folliculogenesis and oocyte maturation for fertility preservation.
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隔离的细胞分泌的细胞外基质蛋白可改善鼠的卵泡发生和卵母细胞的成熟，从而保存生育能力。
DOI：
10.1016/j.actbio.2021.03.041
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发表时间：
2021-09-15
影响因子：
9.7
通讯作者：
Shikanov A
中科院分区：
文献类型：
--
作者：
Tomaszewski CE;DiLillo KM;Baker BM;Arnold KB;Shikanov A
合成基质为模仿天然组织的细胞外基质功能提供了高度的控制和可调性，从而允许在体外研究疾病和发育。在这项研究中，我们用细胞外基质（ECM）螯合肽对可降解聚（乙二醇）水凝胶进行功能化，旨在重现用于卵巢滤泡类器官培养和成熟的天然ECM成分。我们假设 ECM 螯合肽将促进细胞分泌的 ECM 分子的沉积和保留，从而在生物惰性 PEG 水凝胶中重建细胞-基质相互作用。具体而言，与 PEG-Cys（一种机械相似但具有生物惰性的对照）相比，来自抗凝血酶 III (HBP) 的肝素结合肽、源自层粘连蛋白 (AG73) 的硫酸乙酰肝素结合肽、基底膜结合肽 (BMB) 和胎盘生长因子 2 (RRR) 的硫酸乙酰肝素结合区域与 PEG 水凝胶显着改善了卵泡的存活、生长和成熟。对培养卵泡周围的水凝胶进行的免疫组织化学分析证实了层粘连蛋白、I 型胶原蛋白、基底膜聚糖和纤连蛋白在 ECM 隔离水凝胶中的隔离和保留，但在生物惰性 PEG-Cys 水凝胶中则不然。与 PEG-Cys 相比，在 PEG-AG73、PEG-BMB 和 PEG-RRR 中培养的卵泡培养基中已知调节卵泡发育的因子浓度也明显更高。 PEG-AG73 和 PEG-BMB 对于促进卵泡成熟最有利，可能是因为 AG73 和 BMB 模拟对卵泡发育至关重要的基底膜相互作用。在这里，我们表明，用 ECM 螯合肽功能化 PEG 可以使细胞分泌的 ECM 保留在水凝胶内，恢复关键的细胞-基质相互作用并促进全合成培养系统中健康的类器官发育。
Synthetic matrices offer a high degree of control and tunability for mimicking extracellular matrix functions of native tissue, allowing the study of disease and development in vitro. In this study, we functionalized degradable poly(ethylene glycol) hydrogels with extracellular matrix (ECM)-sequestering peptides aiming to recapitulate the native ECM composition for culture and maturation of ovarian follicular organoids. We hypothesized that ECM-sequestering peptides would facilitate deposition and retention of cell-secreted ECM molecules, thereby recreating cell-matrix interactions in otherwise bioinert PEG hydrogels. Specifically, heparin-binding peptide from antithrombin III (HBP), heparan sulfate binding peptide derived from laminin (AG73), basement membrane binder peptide (BMB), and heparan sulfate binding region of placental growth factor 2 (RRR) tethered to a PEG hydrogel significantly improved follicle survival, growth and maturation compared to PEG-Cys, a mechanically similar but biologically inert control. Immunohistochemical analysis of the hydrogel surrounding cultured follicles confirmed sequestration and retention of laminin, collagen I, perlecan and fibronectin in ECM-sequestering hydrogels but not in bioinert PEG-Cys hydrogels. The media from follicles cultured in PEG-AG73, PEG-BMB, and PEG-RRR also had significantly higher concentrations of factors known to regulate follicle development compared to PEG-Cys. PEG-AG73 and PEG-BMB were the most beneficial for promoting follicle maturation, likely because AG73 and BMB mimic basement membrane interactions which are crucial for follicle development. Here we have shown that functionalizing PEG with ECM-sequestering peptides allows cell-secreted ECM to be retained within the hydrogels, restoring critical cell-matrix interactions and promoting healthy organoid development in a fully synthetic culture system.
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影响因子：
6.2
作者：
Cambria E;Renggli K;Ahrens CC;Cook CD;Kroll C;Krueger AT;Imperiali B;Griffith LG
通讯作者：
Griffith LG
DOI：
10.1073/pnas.1214100110
发表时间：
2013-06-18
影响因子：
11.1
作者：
Bian, Liming;Guvendiren, Murat;Burdick, Jason A.
通讯作者：
Burdick, Jason A.
影响因子：
4.8
作者：
Hoffman, MP;Engbring, JA;Kleinman, HK
通讯作者：
Kleinman, HK
影响因子：
2.7
作者：
Irving-Rodgers, Helen F.;Rodgers, Raymond J.
通讯作者：
Rodgers, Raymond J.
DOI：
10.1016/j.bbrc.2004.05.018
发表时间：
2004-06-25
影响因子：
3.1
作者：
Johnson, G;Moore, SW
通讯作者：
Moore, SW