PGS 支架促进骨髓间充质干细胞的体内存活和定向分化,恢复创伤大鼠子宫的形态和功能。
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.
机构信息
Department of Medical Genetics, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433, P. R. China.
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-dimension Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, P. R. China.
出版信息
Adv Healthc Mater. 2019 Mar;8(5):e1801455. doi: 10.1002/adhm.201801455. Epub 2019 Feb 7.
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.
宫腔粘连(IUA)导致生殖雌性哺乳动物不孕和反复流产,通常是由于子宫内膜损伤引起的。然而,目前尚无有效的治疗方法来避免 IUA。骨髓间充质干细胞(BMSCs)是组织再生的重要细胞来源。本研究设计并探索了负载 BMSCs 的弹性聚(甘油癸二酸酯)(PGS)支架预防 IUA 的能力,并比较了 PGS 与聚乳酸-共-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 3D 架构有利于大鼠 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 支架在创伤大鼠子宫模型中显著延长了 BMSCs 的保留时间。更重要的是,PGS/BMSCs 构建体移植后,BMSCs 可以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/BMSCs 或 BMSCs 宫内移植的大鼠相比,PGS/BMSCs 构建体附近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。此外,与 PLGA/BMSCs 和胶原/BMSCs 相比,PGS/BMSCs 移植导致受损子宫的形态恢复更好。PGS/BMSCs 的接受生育能力为 72.2±6.4%,与胶原/BMSCs 相似,但明显高于 PLGA/BMSCs 的 42.3±3.9%。综上所述,PGS/BMSCs 可能是预防 IUA 的一种有前途的候选物。