期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 542, 期 1-2, 页码 82-89出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2018.03.015
关键词
Endothelial progenitor cells; Conditioned medium; Hypoxia; Nanoparticles; Hindlimb ischemia; Angiogenesis
资金
- Regione Toscana
Endothelial progenitor cells (EPCs) contribute to ischemic tissue repair by paracrine secretion up-regulated by hypoxia. In this study we use novel nanoparticles (NPs) as carriers for a controlled release of EPC secretome (CM) to improve their angiogenic properties. The in vivo effect in ischemic hindlimb rat model was evaluated, comparing hypoxic EPC-CM-NPs with hypoxic EPC-CM alone. A proteomic characterization of hypoxic CM and the in vitro effect on endothelial cells (HUVECs) were also performed. Up to 647 protein, 17 of which with angiogenic properties, were upregulated by hypoxia. Moreover, hypoxic EPC-CM significantly promoted capillary-like structures on Matrigel. A significant increase of blood perfusion in ischemic limbs at 2 weeks with EPCCM-loaded NPs as compared to both EPC-CM and control and a significant increase of capillary formation were observed. The use of EPC-CM-NPs significantly improved neoangiogenesis in vivo, underlining the advantages of controlled release in regenerative medicine.
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