Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer

被引：195

作者：

Du, Wei ^{[1
]}

Zhang, Kaiyue ^{[1
]}

Zhang, Shuaiqiang ^{[1
]}

Wang, Ran ^{[1
]}

Nie, Yan ^{[1
]}

Tao, Hongyan ^{[1
]}

Han, Zhibo ^{[2
]}

Liang, Lu ^{[2
]}

Wang, Di ^{[1
]}

Liu, Jianfeng ^{[3
,4
]}

Liu, Na ^{[1
]}

Han, Zhongchao ^{[2
]}

Kong, Deling ^{[5
]}

Zhao, Qiang ^{[5
]}

Li, Zongjin ^{[1
,5
]}

机构：

[1] Nankai Univ, Sch Med, 94 Weijin Rd, Tianjin 300071, Peoples R China

[2] Hlth & Biotech Co, Beijing Inst Hlth & Stem Cells, Beijing, Peoples R China

[3] Chinese Acad Med Sci, Inst Radiat Med, Tianjin Key Lab Mol Nucl Med, Tianjin, Peoples R China

[4] Peking Union Med Coll, Tianjin, Peoples R China

[5] Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Key Lab Bioact Mat,Minist Educ, Tianjin, Peoples R China

来源：

BIOMATERIALS | 2017年 / 133卷

基金：

中国国家自然科学基金;

关键词：

Mesenchymal stem cell(MSC); Exosome; Nitric oxide; Vascular endothelial growth factor (VEGF); miR-126; Angiogenesis; EXTRACELLULAR VESICLES; ANGIOGENESIS; TRANSPLANTATION; ENDOTHELIUM; SECRETION; ISCHEMIA; DELIVERY; CD34(+); GROWTH; INJURY;

D O I：

10.1016/j.biomaterials.2017.04.030

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for the treatment of degenerative diseases or injury and may provide an alternative to cell-based therapy. However, the compositions in MSC-derived exosomes are highly influenced by the microenvironment in which their original cells reside. Here, we hypothesized that a nitric oxide (NO)-releasing polymer can boost the proangiogenic compositions of exosomes and enhance their proangiogenic capacity. Our results demonstrated that exosomes, released from human placenta-derived MSCs (hP-MSCs) by NO stimulation, augment the angiogenic effects of human umbilical vein endothelial cells (HUVECs) in vitro. Moreover, exosomes released from hP-MSCs by NO stimulation revealed superior angiogenic effects and ameliorated limb function in a murine model of hind limb ischemia. Further analysis demonstrated that increased VEGF and miR-126 levels in exosomes released from hP-MSCs by NO stimulation were identified as a novel mechanism contributing to the increased capacity of these exosomes to promote angiogenic processes. In conclusion, designing specific microenvironments for in vitro stem cell culture, such as those containing bioactive material, will facilitate the development of customized exosomes encapsulating a beneficial composition of stem cells for cell-free therapeutic applications. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：70 / 81

页数：12

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