High yield engineered nanovesicles from ADSC with enriched miR-21-5p promote angiogenesis in adipose tissue regeneration

Biomaterials Research

Research Article

Jing Tong¹  Lifeng Chen¹  Zhenxing Wang¹  Rongrong Wang¹  Shan Mou¹  Jiaming Sun¹  Di Sun¹  Jie Yang¹  Aimei Zhong¹  Wei Wang¹ 

[1] Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Wuhan Clinical Research Center for Superficial Organ Reconstruction, 430022, Wuhan, China;

关键词: Engineered nanovesicles;    MSCs;    Angiogenesis;    Adipose tissue regeneration;    miRNAs;   

DOI  :  10.1186/s40824-022-00325-y

 received in 2022-06-23, accepted in 2022-11-18,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundMesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been found to have a great potential for soft tissue repair due to various biological functions, including pro-angiogenesis and low immunogenicity. However, the low yield and heterogeneity of MSC-EVs limited their clinical transformation. This study was designed to develop a novel adipose-derived stem cell engineered nanovesicles (ADSC-NVs) with high production and explore its pro-angiogenetic effect and application in adipose tissue regeneration.MethodsAdipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) were isolated from an EVs-free culture medium for human ADSCs (hADSCs). ADSC-NVs were prepared by sequentially extruding ADSCs followed by iodixanol density gradient ultracentrifugation and were compared with ADSC-EVs in morphology, size distribution, protein contents and yield. The pro-angiogenetic effect of ADSC-NVs in different doses (0, 5, 20 and 80 μg/mL) in vitro was determined using transwell assay, tube formation assay, western blot and qRT-PCR. In vivo, BALB/c nude mice were administered injection of a mixture of fat granules and different dose of ADSC-NVs and grafts were harvested at 12 weeks post-transplantation for further analysis. By analyzing the weight and volume of grafts and histological evaluation, we investigated the effect of ADSC-NVs in vessel formation and adipose tissue regeneration.ResultsOur results showed yield of purified ADSC-NVs was approximately 20 times more than that of ADSC-EVs secreted by the same number of ADSCs. In vitro, both ADSC-NVs and ADSC-EVs exhibited a dose-dependent pro-angiogenetic effect, despite their distinct miRNA profiles. These effects of ADSC-NVs may be mediated by enriched miR-21-5p via PTEN inhibition and PI3K/p-Akt signaling activation. Furthermore, after a mixed injection of ADSC-NVs, vessel formation and adipose regeneration were observed in vivo in fat implants.ConclusionsOur study developed a potent alternative of ADSC-EVs. ADSC-NVs have a high pro-angiogenesis potential and can be used as cell-free therapeutic biomaterials in soft tissue regeneration.

【 授权许可】

CC BY   
© The Author(s) 2022

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