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Abstract：
BACKGROUND: Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.
OBJECTIVE: To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.
METHODS: Human vaginal wall collagen content was assessed by Masson\'s trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.
RESULTS: In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.
CONCLUSIONS: HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.
OBJECTIVE: To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.
METHODS: Human vaginal wall collagen content was assessed by Masson\'s trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed via RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined via functional experiments in vitro. RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.
RESULTS: In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production in vitro. High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.
CONCLUSIONS: HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro. Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.
摘要：
背景：由于盆底组织松弛，盆腔器官脱垂（POP）涉及盆腔器官疝到阴道，阴道结构是一个重要因素。在POP中,阴道壁表现出异常的胶原分布和降低的成纤维细胞水平和功能。POP的复杂病因和在骨盆重建手术中禁止经阴道网状物提出了靶向治疗发展的挑战。人脐带间充质基质细胞（hucMSCs）存在局限性，但它们的外泌体（hucMSC-Exo）是促进成纤维细胞增殖和细胞外基质重塑的有希望的治疗工具。
目的：探讨hucMSC-Exo对原代阴道成纤维细胞功能的影响及其机制。
方法：通过Masson三色和天狼星蓝染色评估人阴道壁胶原含量。通过RNA测序(RNA-seq)评估来自具有和不具有POP的患者的成纤维细胞中的基因表达差异。通过体外功能实验确定hucMSC-Exo对成纤维细胞的作用。联合分析来自暴露于hucMSC-Exo的成纤维细胞的RNA-seq数据和来自hucMSC-Exo的microRNA(miRNA)测序数据以鉴定有效分子。
结果：在POP中，阴道壁胶原分布异常，成纤维细胞1质量和数量降低。用4或6μg/mLhucMSC-Exo抑制POP组成纤维细胞的炎症，刺激原代成纤维细胞生长，和升高的胶原蛋白I（Col1）的体外生产。用hucMSC-Exo处理的成纤维细胞的高通量RNA-seq和hucMSC-Exo的miRNA测序显示，丰富的外泌体miRNA下调基质金属蛋白酶11（MMP11）的表达。
结论：HucMSC-Exo在体外通过促进细胞生长和Col1表达使POP患者原代成纤维细胞的生长和功能正常化。hucMSC-Exo中丰富的miRNA靶向并下调MMP11表达。基于HucMSC-Exo的治疗对于安全有效地治疗POP可能是理想的。
目的：探讨hucMSC-Exo对原代阴道成纤维细胞功能的影响及其机制。
方法：通过Masson三色和天狼星蓝染色评估人阴道壁胶原含量。通过RNA测序(RNA-seq)评估来自具有和不具有POP的患者的成纤维细胞中的基因表达差异。通过体外功能实验确定hucMSC-Exo对成纤维细胞的作用。联合分析来自暴露于hucMSC-Exo的成纤维细胞的RNA-seq数据和来自hucMSC-Exo的microRNA(miRNA)测序数据以鉴定有效分子。
结果：在POP中，阴道壁胶原分布异常，成纤维细胞1质量和数量降低。用4或6μg/mLhucMSC-Exo抑制POP组成纤维细胞的炎症，刺激原代成纤维细胞生长，和升高的胶原蛋白I（Col1）的体外生产。用hucMSC-Exo处理的成纤维细胞的高通量RNA-seq和hucMSC-Exo的miRNA测序显示，丰富的外泌体miRNA下调基质金属蛋白酶11（MMP11）的表达。
结论：HucMSC-Exo在体外通过促进细胞生长和Col1表达使POP患者原代成纤维细胞的生长和功能正常化。hucMSC-Exo中丰富的miRNA靶向并下调MMP11表达。基于HucMSC-Exo的治疗对于安全有效地治疗POP可能是理想的。
