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CD73阳性的小儿尿道间充质干细胞样细胞衍生的小细胞外囊泡刺激血管生成。

CD73-positive pediatric urethral mesenchymal stem-like cell-derived small extracellular vesicles stimulate angiogenesis.

作者信息

Zhang Shilin, Li Jierong, Li Chunjing, Xie Xumin, He Jun, Ling Fengsheng, Li Bowei, Wu Huayan, Li Zhilin, Zhen Jianwei, Liu Guoqing

机构信息

Department of Urology, Foshan Maternity & Child Healthcare Hospital, Foshan 528000, China.

出版信息

Regen Ther. 2023 Dec 14;25:77-84. doi: 10.1016/j.reth.2023.12.002. eCollection 2024 Mar.

DOI:10.1016/j.reth.2023.12.002
PMID:38111468
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10727923/
Abstract

INTRODUCTION

Angiogenesis plays an important role in the repair of urethral injury, and stem cells and their secretomes can promote angiogenesis. We obtained pediatric urethral mesenchymal stem-like cells (PU-MSLCs) in an earlier study. This project studied the pro-angiogenic effect of PU-MSLC-derived small extracellular vesicles (PUMSLC-sEVs) and the underlying mechanisms.

MATERIALS AND METHODS

PUMSLCs and PUMSLC-sEVs were cultivated and identified. Then, biological methods such as the ethynyl deoxyuridine (EdU) incorporation assay, Cell Counting Kit-8 (CCK-8) assay, scratch wound assay, Transwell assay, and tube formation assay were used to study the effect of PUMSLC-sEVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). We explored whether the proangiogenic effect of PUMSLC-sEVs is related to CD73 and whether adenosine (ADO, a CD73 metabolite) promoted angiogenesis. GraphPad Prism 8 software was used for data analysis.

RESULTS

We observed that PUMSLC-sEVs significantly promoted the proliferation, migration, and tube-forming abilities of HUVECs. PUMSLC-sEVs delivered CD73 molecules to HUVECs to promote angiogenesis. The angiogenic ability of HUVECs was enhanced after treatment with extracellular ADO produced by CD73, and PUMSLC-sEVs further promoted angiogenesis by activating Adenosine Receptor A2A (A2AR).

CONCLUSIONS

These observations suggest that PUMSLC-sEVs promote angiogenesis, possibly through activation of the CD73/ADO/A2AR signaling axis.

摘要

引言

血管生成在尿道损伤修复中起重要作用，干细胞及其分泌产物可促进血管生成。我们在早期研究中获得了小儿尿道间充质干细胞样细胞（PU-MSLCs）。本项目研究了PU-MSLC衍生的小细胞外囊泡（PUMSLC-sEVs）的促血管生成作用及其潜在机制。

材料与方法

培养并鉴定PUMSLCs和PUMSLC-sEVs。然后，采用诸如乙炔基脱氧尿苷（EdU）掺入试验、细胞计数试剂盒-8（CCK-8）试验、划痕试验、Transwell试验和管形成试验等生物学方法，研究PUMSLC-sEVs对人脐静脉内皮细胞（HUVECs）增殖、迁移和管形成的影响。我们探讨了PUMSLC-sEVs的促血管生成作用是否与CD73相关，以及腺苷（ADO，一种CD73代谢产物）是否促进血管生成。使用GraphPad Prism 8软件进行数据分析。

结果

我们观察到PUMSLC-sEVs显著促进了HUVECs的增殖、迁移和管形成能力。PUMSLC-sEVs将CD73分子传递给HUVECs以促进血管生成。用CD73产生的细胞外ADO处理后，HUVECs的血管生成能力增强，并且PUMSLC-sEVs通过激活腺苷受体A2A（A2AR）进一步促进血管生成。

结论

这些观察结果表明，PUMSLC-sEVs可能通过激活CD73/ADO/A2AR信号轴促进血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/45054260f8bd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/4e1270409867/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/74f6d6599d72/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/94ce915f2553/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/760e18b45a4c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/be8d0a8d471c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/45054260f8bd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/4e1270409867/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/74f6d6599d72/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/94ce915f2553/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/760e18b45a4c/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/be8d0a8d471c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb71/10727923/45054260f8bd/gr6.jpg

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