Quiñones Edgar Daniel, Wang Mu-Hui, Liu Kuan-Ting, Lu Ting-Yu, Lan Guan-Yu, Lin Yu-Ting, Chen Yu-Liang, Shen Tang-Long, Wu Pei-Hsun, Hsiao Yu-Sheng, Chuang Er-Yuan, Yu Jiashing, Cheng Nai-Chen
Taiwan International Graduate Program, Sustainable Chemical Science & Technology, Academia Sinica, Institute of Chemistry, Taipei 115, Taiwan.
Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan.
Mater Today Bio. 2024 Nov 8;29:101333. doi: 10.1016/j.mtbio.2024.101333. eCollection 2024 Dec.
The management of diabetic wounds presents a considerable challenge within the realm of clinical practice. Cellular-derived nanoparticles, or extracellular vesicles (EV), generated by human adipose-derived stem cells (hASCs) have been investigated as promising candidates for the treatment of diabetic wounds. Nevertheless, limitations on the yield, as well as the qualitative angiogenic properties of the EV produced, have been a persistent issue. In this study, a novel approach involving the use of various cell culture morphologies, such as cell spheroids, on hASC was used to promote both EV yield and qualitative angiogenic properties for clinical use, with an emphasis on the in vivo angiogenic properties exhibited by the EV. Moreover, an increase in the secretion of the EV was confirmed after cell spheroid culture. Furthermore, microRNA(miRNA) analysis of the produced EVs indicated an increase in the presence of wound healing-associated miRNAs on the cell spheroid EV. Analysis of the effectiveness of the treated EVs in vitro indicated a significant promotion of the biological function of fibroblast and endothelial cells, cell migration, and cell proliferation post-cell spheroid EV application. Meanwhile, in vivo experiments on diabetic rats indicated a significant increase in collagen production, re-epithelization, and angiogenesis of the diabetic wound after EV administration. In this investigation, we posit that the use of cell spheroids for the culture of hASC represents a novel approach to enhance the substantial secretion of extracellular vesicles while increasing the angiogenic wound healing properties. This innovation holds promise for augmenting the therapeutic potential of EVs in diabetic wound healing, aligning with the exigencies of clinical applications for these nanoparticles.
糖尿病伤口的管理在临床实践领域面临着相当大的挑战。由人脂肪来源干细胞（hASC）产生的细胞衍生纳米颗粒或细胞外囊泡（EV）已被研究作为治疗糖尿病伤口的有前景的候选物。然而，产量的限制以及所产生的EV的定性血管生成特性一直是个问题。在本研究中，一种涉及在hASC上使用各种细胞培养形态（如细胞球）的新方法被用于提高EV产量和定性血管生成特性以供临床使用，重点是EV所表现出的体内血管生成特性。此外，细胞球培养后证实了EV分泌的增加。此外，对所产生的EV进行的微小RNA（miRNA）分析表明，细胞球EV上与伤口愈合相关的miRNA的存在有所增加。对经处理的EV在体外的有效性分析表明，在应用细胞球EV后，成纤维细胞和内皮细胞的生物学功能、细胞迁移和细胞增殖有显著促进。同时，对糖尿病大鼠的体内实验表明，给予EV后，糖尿病伤口的胶原蛋白产生、再上皮化和血管生成显著增加。在本研究中，我们认为使用细胞球培养hASC是一种新方法，可增强细胞外囊泡的大量分泌，同时增加血管生成性伤口愈合特性。这一创新有望增强EV在糖尿病伤口愈合中的治疗潜力，符合这些纳米颗粒临床应用的迫切需求。
