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Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman's syndrome

查看全文 作　　者：Guangfeng [1]Zhao;Yun [1]Cao;Xianghong [1]Zhu;Xiaoqiu [1]Tang;Lijun [2]Ding;Haixiang [2]Sun;Juan [1]Li;Xinan [1]Li;Chenyan [1]Dai;Tong [1]Ru;Hui [1]Zhu;Jingjie [1]Lu;Caimei [1]Lin;Jingmei [3]Wang;Guijun [2]Yan;Huiyan [1]Wang;Lei [1]Wang;Yimin [1]Dai;Bin [4]Wang;Ruotian [5]Li;Jianwu [6]Dai;Yan [7]Zhou;Yali [1]Hu 高影响力作者 机构地区：[1]Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China;[2]Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China;[3]Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China;[4]Nanjing Center for Stem Cells and Biomaterials, The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008, China;[5]The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China;[6]Instituteof Genetics and Developmental Biology, Chinese Academy of Sciences, Beijung 100190, China;[7]Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences,Eli and Edythe Broad Center of Regeneration Medicine and Stern Cell Research, University of California San Francisco, San Francisco 94143, USA高影响力机构 出　　处：《Science China(Life Sciences)》索引2017年第60卷第4期,共13页高影响力期刊 基　　金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030505);Key research and development program of Jiangsu province (BE2016612), Jiangsu Biobank of Clinical Resources (BM2015004);the Key Laboratory for Maternal-Fetal Medicine from the Health Department of Jiangsu Province, China (XK201102);Project of Nanjing clinical medicine center and the National Natural Science Foundation of China (81401223) 摘　　要：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 ΔNp63 is significantly upregulated in residual epithelial cells of the impaired endometrium in AS; the upregulated-ΔNp63 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 ΔNp63 expression, reverses ΔNp63-induced pathological changes, normalizes the stemness alterations and restores endometrial regeneration. Finally, five patients achieved successful pregnancies and live births. Therefore, we conclude that ΔNp63 is a crucial therapeutic target for AS. This novel treatment significantly improves the outcome for the patients with severe AS. 关 键 词：Asherman’s syndrome ΔNP63 QUIESCENCE endometrial regeneration bone marrow stem cell based therapy
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