title: Transplantation of collagen scaffold with autologous bone marrow mononuclear cells promotes functional endometrium reconstruction via downregulating ΔNp63 expression in Asherman's syndrome.
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.
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Guangfeng
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Tang
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Ding
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Haixiang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Xinan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Chenyan
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Ru
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Jingjie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Caimei
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Guijun
authors.initials: G
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Nanjing Center for Stem Cells and Biomaterials, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
authors.forename: Ruotian
authors.initials: R
authors.lastname: Li
authors.affiliation: Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, China. jwdai@genetics.ac.cn.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, 94143, USA. yzhou@cgl.ucsf.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China. yalihu@nju.edu.cn.
authors.forename: Yali
authors.initials: Y
authors.lastname: Hu
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism*; D017690:Cell Transplantation; D003094:Collagen / Q000378:metabolism*; D015536:Down-Regulation; D004717:Endometrium / Q000473:pathology*; D005260:Female; D006175:Gynatresia / Q000378:metabolism*; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D054457:Tissue Scaffolds; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D003094:Collagen
keywords: Asherman’s syndrome; bone marrow stem cell based therapy; endometrial regeneration; quiescence; ΔNp63