Transplantation of Human Adipose Stem Cells Using Acellular Human Amniotic Membrane Improves Angiogenesis in Injured Endometrial Tissue in a Rat Intrauterine Adhesion Model.

Transplantation of Human Adipose Stem Cells Using Acellular Human Amniotic Membrane Improves Angiogenesis in Injured Endometrial Tissue in a Rat Intrauterine Adhesion Model.
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使用脱细胞人羊膜移植人脂肪干细胞可改善大鼠宫腔粘连模型中受损子宫内膜组织的血管生成

DOI:
10.1177/0963689720952055
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发表时间:
2020-01
影响因子:
3.3
通讯作者:
Huang X
Huang X
中科院分区:
医学4区
文献类型:
--
作者:
Han X;Ma Y;Lu X;Li W;Xia E;Li TC;Zhang H;Huang X

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子宫内膜损伤导致宫腔粘连与子宫内膜再生基底层的广泛损伤有关,是治疗上的一大挑战。人类脂肪干细胞(HASCs)有望在未来的临床上用于损伤子宫内膜组织的个体化治疗。在此,我们观察到无细胞人羊膜(AHAM)的使用显著增加了体外培养的hASCs中血管生成素(Ang)和血管内皮生长因子(VEGF)的表达。三维工程HASC-AHAM移植显著增加了子宫内膜的容受性,与单独使用AHAM治疗的损伤内膜组织相比,移植后损伤内膜组织的子宫内膜厚度增加,子宫内膜腺数量增加,白血病抑制因子蛋白水平升高。此外,HASC-AHAM移植到受损子宫腔后,显著增加了大鼠受损子宫内膜组织中的血管密度。利用EGFP+-HASC-AHAM移植物进行移植,我们证实hASCs在体内损伤的宫腔内维持了较高的Ang和VEGF的蛋白水平。本研究结果提示,基因工程HASC-AHAM移植修复受损子宫内膜组织的能力可能与其通过上调hASCs中血管生成因子的表达来促进血管生成有关。这些发现可能支持使用生物人工移植物进行基于干细胞的个体化治疗子宫内膜疾病。
Endometrial injury resulting in intrauterine adhesion is associated with extensive damage to the regenerative basal layer of the endometrium and represents a major therapeutic challenge. Human adipose stem cells (hASCs) hold promise for future clinical use in the individualized therapy of injured endometrial tissue. Here, we observed that the use of the acellular human amniotic membrane (AHAM) significantly increased the expression of angiogenic factors, including angiogenin (ANG) and vascular endothelial growth factor (VEGF), in hASCs in vitro. The three-dimensional engineered hASC-AHAM grafts significantly increased the endometrial receptivity, as increased endometrial thickness, greater numbers of endometrial glands, and higher protein levels of leukemia inhibitory factor were observed in injured endometrial tissue that was treated with these grafts compared to those detected in injured endometrial tissue that was treated with AHAM alone. In addition, the hASC-AHAM grafts significantly increased the vascular density in the injured endometrial tissue in rats, when transplanted into an injured uterine cavity. Using the EGFP+-hASC-AHAM grafts for transplantation, we confirmed that the hASCs maintained higher protein levels of ANG and VEGF in the injured uterine cavity in vivo. The results of this study suggest that the ability of the engineered hASC-AHAM grafts to repair injured endometrial tissue may be associated with their ability to promote angiogenesis through the upregulated expression of angiogenic factors in hASCs. These findings may support individualized stem cell–based therapy for endometrial disease using bioartificial grafts.
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