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Int. J. Mol. Sci. 2018, 19(2), 529; https://doi.org/10.3390/ijms19020529

Bioreducible Polymer Micelles Based on Acid-Degradable Poly(ethylene glycol)-poly(amino ketal) Enhance the Stromal Cell-Derived Factor-1α Gene Transfection Efficacy and Therapeutic Angiogenesis of Human Adipose-Derived Stem Cells

1
School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Korea
2
Division of Bioengineering, Incheon National University, Incheon 406-772, Korea
3
Department of Chemical Engineering, College of Engineering, Kyung Hee University, Youngin 17104, Korea
4
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
5
Developmental, Regenerative, and Stem Cell Biology Program, Washington University School of Medicine, St. Louis, MO 63110, USA
6
Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
7
Department of Biomedical Science, CHA University, Seongnam 463-400, Korea
*
Authors to whom correspondence should be addressed.
Received: 14 January 2018 / Revised: 5 February 2018 / Accepted: 6 February 2018 / Published: 9 February 2018
(This article belongs to the Special Issue Nano/Micro-Assisted Regenerative Medicine)
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Abstract

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-1α (SDF-1α) 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-1α plasmid DNA. The SDF-1α gene was successfully delivered into human ADSCs (hADSCs) using PEG-PAK micelles. Transfection of SDF-1α increased SDF-1α, 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-1α-transfected hADSCs also showed significantly increased SDF-1α 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. View Full-Text
Keywords: angiogenesis; bioreducible polymer; gene therapy; hADSCs; SDF-1α angiogenesis; bioreducible polymer; gene therapy; hADSCs; SDF-1α
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Lee, T.-J.; Shim, M.S.; Yu, T.; Choi, K.; Kim, D.-I.; Lee, S.-H.; Bhang, S.H. Bioreducible Polymer Micelles Based on Acid-Degradable Poly(ethylene glycol)-poly(amino ketal) Enhance the Stromal Cell-Derived Factor-1α Gene Transfection Efficacy and Therapeutic Angiogenesis of Human Adipose-Derived Stem Cells. Int. J. Mol. Sci. 2018, 19, 529.

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