Abstract
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.
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Acknowledgements
We thank Yaling Li from Department of Obstetrics and Gynecology, the Affiliated Drum Tower Hospital of Nanjing University Medical School for assistance in patient care, Jun Yang from Department of Obstetrics and Gynecology, the Affiliated Drum Tower Hospital of Nanjing University Medical School for tissue section prepare. This work was 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), and Project of Nanjing clinical medicine center and the National Natural Science Foundation of China (81401223).
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Collagen scaffold carried autologous bone marrow mononuclear cells promote endometrial regeneration through downregulating ΔNp63 expression in Asherman’s Syndrome
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Zhao, G., Cao, Y., Zhu, X. et al. Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman’s syndrome. Sci. China Life Sci. 60, 404–416 (2017). https://doi.org/10.1007/s11427-016-0328-y
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DOI: https://doi.org/10.1007/s11427-016-0328-y