ALPL依赖外泌体途径调控BMMSCs诱导内皮细胞管腔形成

doi:10.13701/j.cnki.kqyxyj.2021.05.017

口腔医学研究 ›› 2021, Vol. 37 ›› Issue (5): 462-467.DOI: 10.13701/j.cnki.kqyxyj.2021.05.017

• 口腔干细胞与再生研究 • 上一篇下一篇

ALPL依赖外泌体途径调控BMMSCs诱导内皮细胞管腔形成

董加一¹, 赵疆东², 赵万民³, 刘文佳^3,4*, 李德华^1*

1.军事口腔学国家重点实验室,口腔疾病国家临床医学研究中心,陕西省口腔生物工程技术研究中心,第四军医大学口腔医院种植科陕西西安 710032;
2.第四军医大学航空航天医学系航空航天医学教育部重点实验室陕西西安 710032;
3.军事口腔学国家重点实验室,口腔疾病国家临床医学研究中心,陕西省口腔疾病国际联合研究中心,第四军医大学口腔医院组织病理学教研室陕西西安 710032;
4.西安交通大学第二附属医院,生物诊断治疗国家地方联合工程中心陕西西安 710004

收稿日期:2020-11-30 发布日期:2021-05-17
通讯作者: * 刘文佳,E-mail:wenjia@xiterm.com;李德华,E-mail:lidehua@fmmu.edu.cn
作者简介:董加一(1994~ ),女,北京人,硕士在读,研究方向:干细胞与成血管。
基金资助:
国家自然科学基金重点项目(编号:81970915);陕西省杰出青年基金(编号:2020JC-33)

Role of ALPL in Regulating Tube Formation of Endothelia Cells by Exosomes from BMMSCs

DONG Jiayi¹, ZHAO Jiangdong², ZHAO Wanmin³, LIU Wenjia^3,4*, LI Dehua^1*

1. Department of Dental Implantation, State Key Laboratory of Military Stomatology & National Clinical Research Center For Oral Diseases & Shanxi Clinical Research Center For Oral Disease, Xi'an 710032, China;
2. Research and Development Center for Tissue Engineering, The Fourth Military Medical University, Xi'an 710032, China;
3. The MOE Key Laboratory of Aerospace Medicine,School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China;
4. National&Local Joint Engineering Research Center of Biodiagnosis and Biotherapy,Precision Medicine Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004,China

Received:2020-11-30 Published:2021-05-17

摘要/Abstract

摘要： 目的:探究ALPL基因在骨髓间充质干细胞(BMMSCs)诱导血管内皮细胞(ECs)管腔形成的作用方式。方法:首先对正常人BMMSCs(Nor-hBMMSCs)、低碱性磷酸酯酶症(HPP)患者BMMSCs (HPP-hBMMSCs)进行多向分化鉴定。其次以Nor-hBMMSCs为对照组,HPP-hBMMSCs及通过慢病毒浸染法过表达ALPL基因的HPP-hBMMSCs(HPP-hBMMSCs+Plenti-ALPL)为实验组,通过管腔形成实验检测各组ECs成管腔能力。随后对HPP-hBMMSCs+Plenti-ALPL给予GW4869,比较其与HPP-hBMMSCs组对ECs管腔的形成能力的影响。最后收集Nor-hBMMSCs、HPP-hBMMSCs、HPP-hBMMSCs+Plenti-ALPL来源的外泌体,验证3组细胞释放的外泌体对ECs成管腔能力的影响。结果:ALPL基因突变导致hBMMSCs诱导ECs管腔形成能力明显降低,在HPP-hBMMSCs过表达ALPL可恢复诱导ECs成管腔能力,并证明这一过程通过外泌体途径实现。结论:ALPL基因调控骨髓间充质干细胞诱导血管内皮细胞管腔形成依赖外泌体途径。

关键词: 骨髓间充质干细胞, 外泌体, 碱性磷酸酶, 管腔形成

Abstract: Objective: To explore the effect of ALPL in BMMSCs on endothelia cells (ECs) tube formation. Methods: Multilineage-differentiation was performed on normal human BMMSCs (Nor-hBMMSCs) and HPP patient BMMSCs (HPP-hBMMSCs). Then Nor-hBMMSCs, HPP-hBMMSCs, and ALPL overexpressed HPP-hBMMSCs (HPP+Plenti-ALPL) were cocultured with ECs. The vascular capacity of each groups was measured by tube formation experiment. To block exosomes secretion, HPP+Plenti-ALPL group was administrated with GW4869 before the tube formation ability was measured. To evaluate the tube formation capacity, ECs were treated with exosomes derived from Nor-hBMMSCs, HPP-hBMMSCs, and HPP-hBMMSCs+Plenti-ALPL, respectively. Results: The ALPL deficiency significantly impaired hBMMSCs induced tube formation of ECs. While the angiogenesis capacity of ECs in HPP-hBMMSCs was rescued by overexpression of ALPL, and such function could be blocked by inhibited exosomes secretion. Conclusion: ALPL plays a significant regulatory role in BMMSCs induced tube formation of vascular endothelial cell in an exosomes-dependent manner

Key words: bone marrow mesenchymal stem cells, exosomes, alkaline phosphatase, tube information

董加一, 赵疆东, 赵万民, 刘文佳, 李德华. ALPL依赖外泌体途径调控BMMSCs诱导内皮细胞管腔形成[J]. 口腔医学研究, 2021, 37(5): 462-467.

DONG Jiayi, ZHAO Jiangdong, ZHAO Wanmin, LIU Wenjia, LI Dehua. Role of ALPL in Regulating Tube Formation of Endothelia Cells by Exosomes from BMMSCs[J]. Journal of Oral Science Research, 2021, 37(5): 462-467.

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ALPL依赖外泌体途径调控BMMSCs诱导内皮细胞管腔形成

Role of ALPL in Regulating Tube Formation of Endothelia Cells by Exosomes from BMMSCs

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