Regenerative capacity of trophoblast stem cell-derived extracellular vesicles on mesenchymal stem cells.

IF 11.3 1区 医学 Q1 Medicine
Yoon-Young Go, Chan-Mi Lee, Sung-Won Chae, Jae-Jun Song
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引用次数: 1

Abstract

Background: Human mesenchymal stem cells (MSCs) are therapeutic for clinical applications because of their excellent immunomodulatory and multiple lineage differentiation abilities at tissue injury sites. However, insufficient number of cells and lack of regenerative properties during in vitro expansion still limit the clinical applicability of MSC therapies. Here, we demonstrated a preconditioning strategy with trophoblast stem cell-derived extracellular vesicles (TSC-EVs) to boost the proliferation and regenerative capacity of MSCs.

Methods: We employed cell proliferation analyses such as CCK8 and BrdU assays to determine the proliferation-promoting role of TSC-EVs on MSCs. Osteogenic effects of TSC-EVs on MSCs were assessed by alkaline phosphatase (ALP) activity, calcium assays, and calvarial bone defect animal models. For skin regenerative effects, skin wound mice model was exploited to analyze wound-healing rate in this study, as well as immunofluorescence and histological staining evaluates. We also performed the small RNA profiling and RNA-sequencing analyzes to understand the cellular mechanism of TSC-EVs on MSCs.

Results: TSC-EVs significantly promoted MSC proliferation under xeno-free conditions and facilitated the therapeutic effects of MSCs, including osteogenesis, anti-senescence, and wound healing. Transcriptomic analysis also provided evidence that specific microRNAs in TSC-EVs and differentially expressed genes (DEGs) in TSC-EV-treated MSCs showed the possibility of TSC-EVs triggering the regenerative abilities of MSCs with cytokine interaction. Hence, we found that NGF/Akt signaling mediated the regenerative effects of TSC-EVs on MSCs as a particular cellular signaling pathway.

Conclusion: The results of this study demonstrated the functional properties of TSC-EVs on MSCs for MSC-based therapeutic applications, suggesting that TSC-EVs may serve as a potential preconditioning source for MSC therapy in the clinical field of regenerative medicine.

Abstract Image

Abstract Image

Abstract Image

间充质干细胞上滋养层干细胞来源的细胞外囊泡的再生能力。
背景:人间充质干细胞(MSCs)因其在组织损伤部位具有良好的免疫调节和多谱系分化能力而被应用于临床治疗。然而,在体外扩增过程中细胞数量不足和缺乏再生特性仍然限制了间充质干细胞治疗的临床适用性。在这里,我们展示了滋养层干细胞衍生的细胞外囊泡(tsc - ev)的预处理策略,以促进间充质干细胞的增殖和再生能力。方法:我们采用CCK8和BrdU等细胞增殖分析来确定tsc - ev对MSCs的增殖促进作用。通过碱性磷酸酶(ALP)活性、钙含量测定和颅骨骨缺损动物模型评估tsc - ev对MSCs的成骨作用。在皮肤再生效果方面,本研究采用皮肤创面小鼠模型分析创面愈合率,并进行免疫荧光和组织学染色评价。我们还进行了小RNA分析和RNA测序分析,以了解tsc - ev对MSCs的细胞机制。结果:在无异种条件下,tsc - ev显著促进MSC增殖,促进MSCs的治疗作用,包括成骨、抗衰老和伤口愈合。转录组学分析也提供了证据,表明tsc - ev中的特异性microrna和tsc - ev处理的MSCs中的差异表达基因(DEGs)表明tsc - ev可能通过细胞因子相互作用触发MSCs的再生能力。因此,我们发现NGF/Akt信号通路作为一种特殊的细胞信号通路介导tsc - ev对MSCs的再生作用。结论:本研究结果证明了tsc - ev对MSC的功能特性,可用于基于MSC的治疗应用,提示tsc - ev可能在再生医学临床领域作为MSC治疗的潜在预处理源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomaterials Research
Biomaterials Research Medicine-Medicine (miscellaneous)
CiteScore
10.20
自引率
3.50%
发文量
63
审稿时长
30 days
期刊介绍: Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.
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