Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition

被引：35

作者：

Aday, Sezin ^{[1
,2
,3
,4
]}

Zoldan, Janet ^{[5
]}

Besnier, Marie ^{[4
]}

Carreto, Laura ^{[6
]}

Saif, Jaimy ^{[4
]}

Fernandes, Rui ^{[7
]}

Santos, Tiago ^{[8
]}

Bernardino, Liliana ^{[8
]}

Langer, Robert ^{[3
]}

Emanueli, Costanza ^{[4
,9
]}

Ferreira, Lino ^{[1
,2
]}

机构：

[1] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal

[2] Univ Coimbra, Fac Med, P-3000548 Coimbra, Portugal

[3] MIT, Dept Chem Engn, Cambridge, MA 02139 USA

[4] Univ Bristol, Bristol Heart Inst, Sch Clin Sci, Bristol BS2 8HW, Avon, England

[5] Univ Texas Austin, Cockrell Sch Engn, Dept Biomed Engn, Austin, TX 78712 USA

[6] Univ Aveiro, P-3810193 Aveiro, Portugal

[7] Univ Porto, IBMC I3S, HEMS, P-4200135 Oporto, Portugal

[8] Univ Beira Interior, Fac Hlth Sci, Hlth Sci Res Ctr, P-6201506 Covilha, Portugal

[9] Imperial Coll London, Natl Heart & Lung Inst, Hammersmith Campus, London SW7 2AZ, England

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

THERAPEUTIC ANGIOGENESIS; ISCHEMIC DISEASE; VEGF; EXPRESSION; PHOSPHORYLATION; VASCULOGENESIS; ACTIVATION; SURFACES; CLUSTER; DEATH;

D O I：

10.1038/s41467-017-00746-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy. Here, we report a pro-survival approach based on VEGF-immobilized microparticles (VEGF-MPs). VEGF-MPs prolong VEGFR-2 and Akt phosphorylation in cord blood-derived late outgrowth endothelial progenitor cells (OEPCs). In vivo, OEPC aggregates containing VEGF-MPs show higher survival than those treated with sVEGF. Additionally, VEGF-MPs decrease miR-17 expression in OEPCs, thus increasing the expression of its target genes CDKN1A and ZNF652. The therapeutic effect of OEPCs is improved in vivo by inhibiting miR-17. Overall, our data show an experimental approach to improve therapeutic efficacy of proangiogenic cells for the treatment of ischemic diseases.

引用

页数：14

共 50 条

[1]

Inflammatory modulation of stem cells by Magnetic Resonance Imaging (MRI)-detectable nanoparticles [J].