دورية أكاديمية

Non-viral gene delivery of HIF-1α promotes angiogenesis in human adipose-derived stem cells.

التفاصيل البيبلوغرافية
العنوان: Non-viral gene delivery of HIF-1α promotes angiogenesis in human adipose-derived stem cells.
المؤلفون: Est-Witte SE; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: sest1@jhmi.edu., Farris AL; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: afarris2@jhu.edu., Tzeng SY; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: stzeng1@jhmi.edu., Hutton DL; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: daphne.hosmane@gmail.com., Gong DH; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: dgong3@jhu.edu., Calabresi KG; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: kcalabr2@jhu.edu., Grayson WL; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA. Electronic address: wgrayson@jhmi.edu., Green JJ; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Oncology and Bloomberg~Kimmel Immunotherapy Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: green@jhu.edu.
المصدر: Acta biomaterialia [Acta Biomater] 2020 Sep 01; Vol. 113, pp. 279-288. Date of Electronic Publication: 2020 Jul 02.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: England NLM ID: 101233144 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-7568 (Electronic) Linking ISSN: 17427061 NLM ISO Abbreviation: Acta Biomater Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Kidlington, Oxford, UK : Elsevier, c2004-
مواضيع طبية MeSH: Gene Transfer Techniques* , Genetic Therapy* , Hypoxia-Inducible Factor 1, alpha Subunit*/genetics, Adipose Tissue ; Humans ; Stem Cells ; Transfection
مستخلص: Stable and mature vascular formation is a current challenge in engineering functional tissues. Transient, non-viral gene delivery presents a unique platform for delivering genetic information to cells for tissue engineering purposes and to restore blood flow to ischemic tissue. The formation of new blood vessels can be induced by upregulation of hypoxia-inducible factor-1α (HIF-1), among other factors. We hypothesized that biodegradable polymers could be used to efficiently deliver the HIF-1α gene to human adipose-derived stromal/stem cells (hASCs) and that this treatment could recruit an existing endogenous endothelial cell population to induce angiogenesis in a 3D cell construct in vitro. In this study, end-modified poly(β-amino ester) (PBAE) nanocomplexes were first optimized for transfection of hASCs and a new biodegradable polymer with increased hydrophobicity and secondary amine structures, N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine end-modified poly(1,4-butanediol diacrylate-co-4-amino-1-butanol), was found to be most effective. Optimal PBAE nanocomplexes had a hydrodynamic diameter of approximately 140 nm and had a zeta potential of 30 mV. The PBAE polymer self-assembled with HIF-1α plasmid DNA and treatment of hASCs with these nanocomplexes induced 3D vascularization. Cells transfected with this polymer-DNA complex were found to have 10 6 -fold upregulation HIF-1α expression, an approximately 2-fold increase in secreted VEGF, and caused the formation of vessel tubules compared to an untransfected control. These gene therapy biomaterials may be useful for regenerative medicine. STATEMENT OF SIGNIFICANCE: Not only is the formation of stable vasculature a challenge for engineering human tissues in vitro, but it is also of valuable interest to clinical applications such as peripheral artery disease. Previous studies using HIF-1α to induce vascular formation have been limited by the necessity of hypoxic chambers. It would be advantageous to simulate endogenous responses to hypoxia without the need for physical hypoxia. In this study, 3D vascular formation was shown to be inducible through non-viral gene delivery of HIF-1α with new polymeric nanocomplexes. A biodegradable polymer N'-(3-aminopropyl)-N,N-dimethylpropane-1,3-diamine end-modified poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) demonstrates improved transfection of human adipose-derived stem cells. This nanobiotechnology could be a promising strategy for the creation of vasculature for tissue engineering and clinical applications.
Competing Interests: Declaration of Competing Interest Jordan Green and Stephany Tzeng are inventors on patents related to the polymer technology discussed in this manuscript.
(Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
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معلومات مُعتمدة: T32 GM007057 United States GM NIGMS NIH HHS; R01 EB022148 United States EB NIBIB NIH HHS; F31 AR075368 United States AR NIAMS NIH HHS; S10 OD016374 United States OD NIH HHS; R01 CA228133 United States CA NCI NIH HHS; P41 EB028239 United States EB NIBIB NIH HHS
فهرسة مساهمة: Keywords: Angiogenesis; Gene delivery; Hypoxia-inducible factor 1; Stem cells; Tissue engineering
المشرفين على المادة: 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
تواريخ الأحداث: Date Created: 20200706 Date Completed: 20210510 Latest Revision: 20240331
رمز التحديث: 20240331
مُعرف محوري في PubMed: PMC8035702
DOI: 10.1016/j.actbio.2020.06.042
PMID: 32623098
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-7568
DOI:10.1016/j.actbio.2020.06.042