Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman's syndrome
Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman's syndrome
复制标题
用自体骨髓单核细胞移植胶原支架通过下调 Asherman 综合征中的 αNp63 表达促进功能性子宫内膜重建。
DOI：
10.1007/s11427-016-0328-y
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发表时间：
2017-04-01
影响因子：
9.1
通讯作者：
Hu, Yali
中科院分区：
文献类型：
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作者：
Zhao, Guangfeng;Cao, Yun;Hu, Yali
Asherman综合征(AS)是一种表现为子宫内膜再生障碍的常见病。然而，对于AS患者这种无再生子宫内膜的分子特征以及如何重建AS患者的功能性子宫内膜，目前还知之甚少。在此，我们报告了Delta Np63在AS受损的子宫内膜残留上皮细胞中显著上调；上调的Delta Np63诱导子宫内膜静止和干性改变。重要的是，我们证明了将高密度的负载胶原支架的自体骨髓单个核细胞(BMNCs)移植到AS患者的子宫内壁上，下调了Delta Np63的表达，逆转了Delta Np63诱导的病理变化，使干性改变正常化，并恢复了子宫内膜的再生。最后，5名患者成功怀孕和活产。因此，我们认为Delta Np63是AS的重要治疗靶点。这一新的治疗方法显著改善了重症AS患者的预后。
Asherman's syndrome (AS) is a common disease that presents endometrial regeneration disorder. However, little is known about its molecular features of this aregenerative endometrium in AS and how to reconstruct the functioning endometrium for the patients with AS. Here, we report that Delta Np63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-Delta Np63 induces endometrial quiescence and alteration of stemness. Importantly, we demonstrate that engrafting high density of autologous bone marrow mononuclear cells (BMNCs) loaded in collagen scaffold onto the uterine lining of patients with AS downregulates Delta Np63 expression, reverses Delta Np63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that Delta Np63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS.