Transplantation of human endometrial perivascular cells with elevated CYR61 expression induces angiogenesis and promotes repair of a full-thickness uterine injury in rat

Autor: Hairong Li, Xin’an Li, Zhongxun Li, Yong Liu, Qiang Diao, Haixiang Sun, Yimin Dai, Lijun Ding, Fei Yu, Bruno Péault, Yali Hu, Huaijun Zhou, Guijun Yan, Xiaoqiang Sheng, Xin Zhen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Angiogenesis
Uterus
Fluorescent Antibody Technique
Medicine (miscellaneous)
Scars
Endometrium
Neovascularization
0302 clinical medicine
Pregnancy
Tandem Mass Spectrometry
lcsh:QD415-436
Cells
Cultured
Endometrial perivascular cells
lcsh:R5-920
Chemistry
CYR61
Cell Differentiation
Uterine horns
Flow Cytometry
Immunohistochemistry
medicine.anatomical_structure
030220 oncology & carcinogenesis
Myometrium
Molecular Medicine
Female
Collagen
medicine.symptom
lcsh:Medicine (General)
Neovascularization
Physiologic
Enzyme-Linked Immunosorbent Assay
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Andrology
lcsh:Biochemistry
03 medical and health sciences
medicine
Animals
Humans
Regeneration
Research
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Rats
Transplantation
030104 developmental biology
Fertility
Uterine injury
Chromatography
Liquid
Cysteine-Rich Protein 61
Zdroj: Stem Cell Research & Therapy, Vol 10, Iss 1, Pp 1-16 (2019)
Stem Cell Research & Therapy
ISSN: 1757-6512
DOI: 10.1186/s13287-019-1272-3
Popis: Background Disruptions of angiogenesis can have a significant effect on the healing of uterine scars. Human endometrial perivascular cells (CD146+PDGFRβ+) function as stem cells in the endometrium. Cysteine-rich angiogenic inducer 61 (CYR61) plays an important role in vascular development. The purpose of this study was to observe the effects of the transplantation of human endometrial perivascular cells (En-PSCs) overexpressing CYR61 on structural and functional regeneration in rat models of partial full-thickness uterine excision. Methods We first sorted human En-PSCs from endometrial single-cell suspensions by flow cytometry. Human En-PSCs expressing low or high levels of CYR61 were then generated via transfection with a CYR61-specific small interfering ribonucleic acid (si-CYR61) construct or overexpression plasmid. To establish a rat model of uterine injury, a subset of uterine wall was then resected from each uterine horn in experimental animals. Female rats were randomly assigned to five groups, including a sham-operated group and four repair groups that received either PBS loaded on a collagen scaffold (collagen/PBS), En-PSCs loaded on a collagen scaffold (collagen/En-PSCs), En-PSCs with low CYR61 expression loaded on a collagen scaffold (collagen/si-CYR61 En-PSCs), and En-PSCs overexpressing CYR61 loaded on a collagen scaffold (collagen/ov-CYR61 En-PSCs). These indicated constructs were sutured in the injured uterine area to replace the excised segment. On days 30 and 90 after transplantation, a subset of rats in each group was sacrificed, and uterine tissue was recovered and serially sectioned. Hematoxylin and eosin staining and immunohistochemical staining were then performed. Finally, the remaining rats of each group were mated with fertile male rats on day 90 for a 2-week period. Results Sorted En-PSCs expressed all recognized markers of mesenchymal stem cells (MSCs), including CD10, CD13, CD44, CD73, CD90, and CD105, and exhibited differentiation potential toward adipocytes, osteoblasts, and neuron-like cells. Compared with En-PSCs and En-PSCs with low CYR61 expression, En-PSCs with elevated CYR61 expression enhanced angiogenesis by in vitro co-culture assays. At day 90 after transplantation, blood vessel density in the collagen/ov-CYR61 En-PSCs group (11.667 ± 1.287) was greater than that in the collagen/En-PSCs group (7.167 ± 0.672) (P
Databáze: OpenAIRE
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