https://scholars.lib.ntu.edu.tw/handle/123456789/524382
標題: | Effective naked plasmid DNA delivery into stem cells by microextrusion-based transient-transfection system for in situ cardiac repair | 作者: | Huang, N.-C. CHII-MING LEE SHAN-HUI HSU |
公開日期: | 2020 | 出版社: | Elsevier B.V. | 卷: | 22 | 期: | 2 | 起(迄)頁: | 70-81 | 來源出版物: | Cytotherapy | 摘要: | Background aims. Combining the use of transfection reagents and physical methods can markedly improve the efficiency of gene delivery; however, such methods often cause cell damage. Additionally, naked plasmids without any vector or physical stimulation are difficult to deliver into stem cells. In this study, we demonstrate a simple and rapid method to simultaneously facilitate efficient in situ naked gene delivery and form a bioactive hydrogel scaffold. Methods. Transfecting naked GATA binding protein 4 (GATA4) plasmids into human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) by co-extruding naked plasmids and hUC-MSCs with a biomimetic and negatively charged water-based biodegradable thermo-responsive polyurethane (PU) hydrogel through a microextrusion-based transient-transfection system can upregulate the other cardiac marker genes. Results. The PU hydrogels with optimized physicochemical properties (such as hard-soft segment composition, size, hardness and thermal gelation) induced GATA4-transfected hUC-MSCs to express the cardiac marker proteins and then differentiated into cardiomyocyte-like cells in 15 days. We further demonstrated that GATA4-transfected hUC-MSCs in PU hydrogel were capable of in situ revival of heart function in zebrafish in 30 days. Conclusions. Our results suggest that hUC-MSCs and naked plasmids encapsulated in PU hydrogels might represent a new strategy for in situ tissue therapy using the microextrusion-based transient-transfection system described here. This transfection system is simple, effective and safer than conventional technologies. ? 2019 International Society for Cell and Gene Therapy |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078781078&doi=10.1016%2fj.jcyt.2019.12.003&partnerID=40&md5=8431f4645d50c110bb731fbcff3b5e14 https://scholars.lib.ntu.edu.tw/handle/123456789/524382 |
ISSN: | 1465-3249 | DOI: | 10.1016/j.jcyt.2019.12.003 | SDG/關鍵字: | homeobox protein Nkx-2.5; myocyte enhancer factor 2; myosin heavy chain; myosin heavy chain 6; plasmid DNA; polyurethan; transcription factor GATA 4; transcription factor TBX5; troponin T; troponin T2; unclassified drug; DNA; GATA4 protein, human; polyurethan; transcription factor GATA 4; adult; animal cell; animal experiment; animal model; animal tissue; Article; biological therapy; biomimetics; cell structure; cell viability; controlled study; DNA content; gelation; gene targeting; gene therapy; hardness; heart disease; heart function; heart size; histology; human; human cell; hydrodynamics; hydrogel; marker gene; mesenchymal stem cell; nonhuman; nuclear reprogramming; phase transition; photon correlation spectroscopy; physical stimulation; priority journal; tissue differentiation; tissue repair; trabecular thickness; transient transfection; umbilical cord blood cell; zebra fish; zeta potential; animal; biological therapy; cardiac muscle cell; cytology; gene therapy; genetic transfection; genetics; growth, development and aging; heart; mesenchymal stem cell; metabolism; pharmacology; plasmid; procedures; umbilical cord; Animals; Cell- and Tissue-Based Therapy; Cellular Reprogramming; DNA; GATA4 Transcription Factor; Genetic Therapy; Heart; Hydrogels; Mesenchymal Stem Cells; Myocytes, Cardiac; Plasmids; Polyurethanes; Transfection; Umbilical Cord; Zebrafish |
顯示於: | 醫學系 |
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