Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 19, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/ijms19020529
Keywords
angiogenesis; bioreducible polymer; gene therapy; hADSCs; SDF-1
Funding
- National Research Foundation of Korea (NRF) grant - Korea government (MSIP) [NRF-2015R1C1A1A01055224, NRF-2016R1A2A1A05004987]
- Kyung Hee University [KHU-20150516]
- Korea Health Technology RD Project [HI17C1728]
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Adipose-derived stem cells (ADSCs) have the potential to treat ischemic diseases. In general, ADSCs facilitate angiogenesis by secreting various pro-angiogenic growth factors. However, transplanted ADSCs have a low therapeutic efficacy in ischemic tissues due to their poor engraftment and low viability. Stromal cell-derived factor-1 (SDF-1) improves the survival rate of stem cells transplanted into ischemic regions. In this study, we developed acid-degradable poly(ethylene glycol)-poly(amino ketal) (PEG-PAK)-based micelles for efficient intracellular delivery of SDF-1 plasmid DNA. The SDF-1 gene was successfully delivered into human ADSCs (hADSCs) using PEG-PAK micelles. Transfection of SDF-1 increased SDF-1, vascular endothelial growth factor, and basic fibroblast growth factor gene expression and decreased apoptotic activity in hADSCs cultured under hypoxic conditions in comparison with conventional gene transfection using polyethylenimine. SDF-1-transfected hADSCs also showed significantly increased SDF-1 and VEGF expression together with reduced apoptotic activity at 4 weeks after transplantation into mouse ischemic hindlimbs. Consequently, these cells improved angiogenesis in ischemic hindlimb regions. These PEG-PAK micelles may lead to the development of a novel therapeutic modality for ischemic diseases based on an acid-degradable polymer specialized for gene delivery.
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