Modulating endothelial cell dynamics in fat grafting: the impact of DLL4 siRNA via adipose stem cell extracellular vesicles.

IF 5 2区 生物学 Q2 CELL BIOLOGY
Sen-Lin Deng, Qiang Fu, Qing Liu, Fu-Jun Huang, Miao Zhang, Xun Zhou
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引用次数: 0

Abstract

In the context of improving the efficacy of autologous fat grafts (AFGs) in reconstructive surgery, this study delineates the novel use of adipose-derived mesenchymal stem cells (ADSCs) and their extracellular vesicles (EVs) as vehicles for delivering delta-like ligand 4 (DLL4) siRNA. The aim was to inhibit DLL4, a gene identified through transcriptome analysis as a critical player in the vascular endothelial cells of AFG tissues, thereby negatively affecting endothelial cell functions and graft survival through the Notch signaling pathway. By engineering ADSC EVs to carry DLL4 siRNA (ADSC EVs-siDLL4), the research demonstrated a marked improvement in endothelial cell proliferation, migration, and lumen formation, and enhanced angiogenesis in vivo, leading to a significant increase in the survival rate of AFGs. This approach presents a significant advancement in the field of tissue engineering and regenerative medicine, offering a potential method to overcome the limitations of current fat grafting techniques.NEW & NOTEWORTHY This study introduces a groundbreaking method for enhancing autologous fat graft survival using adipose-derived stem cell extracellular vesicles (ADSC EVs) to deliver DLL4 siRNA. By targeting the delta-like ligand 4 (DLL4) gene, crucial in endothelial cell dynamics, this innovative approach significantly improves endothelial cell functions and angiogenesis, marking a substantial advancement in tissue engineering and regenerative medicine.

调节脂肪移植中的内皮细胞动力学:DLL4 siRNA 通过脂肪干细胞胞外囊泡的影响
为了提高自体脂肪移植(AFG)在整形手术中的疗效,本研究界定了脂肪间充质干细胞(ADSCs)及其细胞外囊泡(EVs)作为递送 DLL4 siRNA 载体的新用途。DLL4是通过转录组分析确定的AFG组织血管内皮细胞中的一个关键基因,目的是抑制DLL4,从而通过Notch信号通路对内皮细胞功能和移植物存活产生负面影响。通过对携带 DLL4 siRNA 的 ADSC EVs(ADSC EVs-siDLL4)进行工程化处理,研究表明内皮细胞的增殖、迁移和管腔形成得到了明显改善,体内血管生成也得到了增强,从而显著提高了 AFG 的存活率。这种方法是组织工程和再生医学领域的一大进步,为克服当前脂肪移植技术的局限性提供了一种潜在的方法。
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来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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