PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus
PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus
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PGS支架促进骨髓间充质干细胞体内存活和定向分化，恢复受损大鼠子宫的形态和功能
DOI：
10.1002/adhm.201801455
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发表时间：
2019-03-07
影响因子：
10
通讯作者：
Sun, Shuhan
中科院分区：
文献类型：
--
作者：
Xiao, Bang;Yang, Wenjun;Sun, Shuhan
子宫内粘连（IUA）是导致雌性哺乳动物不孕和反复流产的主要原因。然而，没有有效的治疗方法来避免IUA。骨髓间充质干细胞是组织再生的重要细胞来源。本研究设计并探索了负载BMSC的弹性聚（癸二酸甘油酯）（PGS）支架预防IUA的能力，并比较了PGS与聚（乳酸-羟基乙酸）（PLGA）和胶原支架在恢复受损大鼠子宫中的作用。PGS支架提供的三维结构有利于大鼠BMSCs的附着和生长。体内生物发光成像显示，与直接BMSC宫内注射、PLGA和胶原支架相比，PGS支架显著延长了BMSC在损伤大鼠子宫模型中的滞留时间。更重要的是，BMSCs移植后可直接分化为子宫内膜基质细胞，而PLGA/BMSCs和胶原/BMSCs则不能。研究发现，与接受PLGA/BMSCs、胶原蛋白/BMSCs或BMSCs宫内移植的大鼠相比，PGS/BMSCs构建体邻近的损伤子宫内膜中转化生长因子β1（TGF-β1）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子和胰岛素样生长因子的水平更高。PGS/BMSCs移植修复子宫缺损的效果优于PLGA/BMSCs和胶原/BMSCs。PGS/BMSCs的受精率为72.2 ± 6.4%，与胶原/BMSCs相近，但明显高于PLGA/BMSCs的42.3 ± 3.9%。总之，PGS/BMSCs可能是预防IUA的有希望的候选者。
Intrauterine adhesion (IUA) causing infertility and recurrent miscarriage of reproductive female mammals usually results from endometrium injury. Nevertheless, there is no efficient therapeutic method to avoid IUA. Bone marrow derived mesenchymal stem cells (BMSCs) are an important cell source for tissue regeneration. This study designs and explores the ability of BMSC‐loaded elastic poly(glycerol sebacate) (PGS) scaffold to prevent IUA and compares the effect of PGS with poly(lactic‐co‐glycolic acid) (PLGA) and collagen scaffolds in resumption of damaged rat uteruses. The 3D architecture provided by PGS scaffolds favors the attachment and growth of rat BMSCs. In vivo bioluminescence imaging shows that compared with direct BMSC intrauterine injection, PLGA, and collagen scaffolds, the PGS scaffold significantly prolongs the retention time of BMSCs in a wounded rat uterus model. More importantly, BMSCs can directly differentiate into endometrial stromal cells after transplantation of PGS/BMSCs constructs, but not PLGA/BMSCs and collagen/BMSCs. It is found that the level of transforming growth factor β1 (TGF‐β1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and insulin‐like growth factors in the injured endometrium adjacent to PGS/BMSCs constructs is higher than those of rats receiving PLGA/BMSCs, collagen/BMSCs, or BMSCs intrauterine transplantation. Besides, transplantation of PGS/BMSCs leads to better morphology recovery of the damaged uterus than PLGA/BMSCs and collagen/BMSCs. The receptive fertility of PGS/BMSCs is 72.2 ± 6.4%, similar to the one of collagen/BMSCs, but significantly higher than 42.3 ± 3.9% in PLGA/BMSCs. Taken together, PGS/BMSCs may be a promising candidate for preventing IUA.