HIF-prolyl hydroxylase 2 silencing using siRNA delivered by MRI-visible nanoparticles improves therapy efficacy of transplanted EPCs for ischemic stroke
Copyright © 2018. Published by Elsevier Ltd..
Endothelial progenitor cell (EPC)-based therapy has brought potential benefits to stroke patients as an important restorative therapeutics. However, its efficacy is limited by poor migration and survival ability. Here, we found out that hif-prolyl hydroxylase 2 (PHD2) silencing could enhance the migration and survival ability of EPCs which could improve the therapy efficacy for ischemic stroke. We successfully developed a siRNA delivery system, which could achieve siRNA delivery and EPCs tracking with magnetic resonance imaging (MRI) simultaneously. Besides, combining MRI and bioluminescence imaging (BLI), we successfully observed full temporal profile of EPCs dynamics in vivo. Furthermore, we found out that PHD2 silencing in EPCs elevated the expression of C-X-C chemokine receptor type 4 (CXCR4) and hypoxia-inducible factor 1α (HIF-1α), which enhanced the migration and survival ability of EPCs respectively. Significantly decreased infarct volume, functional deficits and increased fractional anisotrophy (FA) value, fiber counts were observed in the siPHD2-EPCs (EPCs transfected with siRNA targeting PHD2) group. What's more, higher level of BNDF, CD31, DCX, NeuN and MBP were also observed in the siPHD2-EPCs group. Altogether, our study provides an effective method to improve EPC-based therapy efficacy for ischemic stroke.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:197 |
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| Enthalten in: |
Biomaterials - 197(2019) vom: 30. März, Seite 229-243 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Congxiao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.05.2020 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biomaterials.2018.05.053 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Wang, Congxiao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HIF-prolyl hydroxylase 2 silencing using siRNA delivered by MRI-visible nanoparticles improves therapy efficacy of transplanted EPCs for ischemic stroke |
| 264 | 1 | |c 2019 | |
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| 520 | |a Copyright © 2018. Published by Elsevier Ltd. | ||
| 520 | |a Endothelial progenitor cell (EPC)-based therapy has brought potential benefits to stroke patients as an important restorative therapeutics. However, its efficacy is limited by poor migration and survival ability. Here, we found out that hif-prolyl hydroxylase 2 (PHD2) silencing could enhance the migration and survival ability of EPCs which could improve the therapy efficacy for ischemic stroke. We successfully developed a siRNA delivery system, which could achieve siRNA delivery and EPCs tracking with magnetic resonance imaging (MRI) simultaneously. Besides, combining MRI and bioluminescence imaging (BLI), we successfully observed full temporal profile of EPCs dynamics in vivo. Furthermore, we found out that PHD2 silencing in EPCs elevated the expression of C-X-C chemokine receptor type 4 (CXCR4) and hypoxia-inducible factor 1α (HIF-1α), which enhanced the migration and survival ability of EPCs respectively. Significantly decreased infarct volume, functional deficits and increased fractional anisotrophy (FA) value, fiber counts were observed in the siPHD2-EPCs (EPCs transfected with siRNA targeting PHD2) group. What's more, higher level of BNDF, CD31, DCX, NeuN and MBP were also observed in the siPHD2-EPCs group. Altogether, our study provides an effective method to improve EPC-based therapy efficacy for ischemic stroke | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a EPCs | |
| 650 | 4 | |a HIF-1α | |
| 650 | 4 | |a Imaging | |
| 650 | 4 | |a Nanoparticles | |
| 650 | 4 | |a PHD2 | |
| 650 | 4 | |a Stroke | |
| 650 | 7 | |a Dcx protein, mouse |2 NLM | |
| 650 | 7 | |a Doublecortin Protein |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
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| 650 | 7 | |a Hypoxia-Inducible Factor-Proline Dioxygenases |2 NLM | |
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| 700 | 1 | |a Lin, Gan |e verfasserin |4 aut | |
| 700 | 1 | |a Luan, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Pei-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Ju, Shenghong |e verfasserin |4 aut | |
| 700 | 1 | |a Teng, Gao-Jun |e verfasserin |4 aut | |
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