Kusumo M Hidayat Budi, Prayitno Adi, Laqif Abdurahman
Doctoral program of Medical Sciences, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.
Department of Surgery, Faculty of Medicine, Universitas Muhammadiyah Purwokerto, Purwokerto, Indonesia.
Arch Med Sci. 2024 Oct 30;20(5):1556-1566. doi: 10.5114/aoms/183465. eCollection 2024.
Mesenchymal stem cells (MSCs) have promising regenerative properties in tissue repair and anti-inflammatory responses. This study aimed to investigate the effects of MSCs and their combination with micronized purified flavonoid fraction (MPFF) in a croton oil-induced hemorrhoids model on tissue edema, inflammation, and underlying molecular mechanisms.
MSCs were isolated and characterized for their adherence, differentiation capacity, and immunophenotyping. Croton oil-induced hemorrhoid mouse models were established to assess tissue edema, inflammation, tumor necrosis factor (TNF-α) expression, transforming growth factor-β (TGF-β) expression, collagen ratio, and MMP-9 activity. The effects of MSCs and their combination with MPFF (diosmin-hesperidin) were evaluated through histological examinations, western blot analysis, and gelatin zymography.
Characterization confirmed the MSCs' plastic adherence, osteogenic differentiation potential, and immunophenotype (positive for CD90 and CD29, negative for CD45 and CD31). Treatment with MSCs alone or in combination with MPFF significantly reduced tissue edema, inflammation, TNF-α expression, and MMP-9 activity. Additionally, MSCs increased TGF-β expression, and collagen type I/III ratio, and accelerated wound healing by resolving inflammation.
These findings suggest that MSCs play a crucial role in modulating TNF-α, TGF-β, collagen remodeling, and MMP-9 activity, highlighting their promising role in hemorrhoid treatment and wound healing processes. Further research is warranted to fully elucidate the intricate mechanisms and optimize MSC-based therapies for clinical applications in hemorrhoidal disease management.
间充质干细胞(MSCs)在组织修复和抗炎反应方面具有良好的再生特性。本研究旨在探讨间充质干细胞及其与微粉化纯化黄酮组分(MPFF)联合应用于巴豆油诱导的痔疮模型中对组织水肿、炎症及潜在分子机制的影响。
分离间充质干细胞并对其贴壁能力、分化能力和免疫表型进行鉴定。建立巴豆油诱导的痔疮小鼠模型,以评估组织水肿、炎症、肿瘤坏死因子(TNF-α)表达、转化生长因子-β(TGF-β)表达、胶原蛋白比例和基质金属蛋白酶-9(MMP-9)活性。通过组织学检查、蛋白质免疫印迹分析和明胶酶谱法评估间充质干细胞及其与MPFF(地奥司明-橙皮苷)联合应用的效果。
鉴定证实间充质干细胞具有贴壁能力、成骨分化潜能和免疫表型(CD90和CD29阳性,CD45和CD31阴性)。单独使用间充质干细胞或与MPFF联合治疗可显著减轻组织水肿、炎症、TNF-α表达和MMP-9活性。此外,间充质干细胞可增加TGF-β表达和I/III型胶原蛋白比例,并通过消除炎症加速伤口愈合。
这些发现表明间充质干细胞在调节TNF-α、TGF-β、胶原蛋白重塑和MMP-9活性方面发挥着关键作用,凸显了它们在痔疮治疗和伤口愈合过程中的潜在作用。有必要进一步研究以充分阐明其复杂机制,并优化基于间充质干细胞的疗法,用于痔疮疾病管理的临床应用。