Instructive nanofiber scaffolds with VEGF create a microenvironment for arteriogenesis and cardiac repair
Autor: | Da Ching Tsai, Chwan Yau Luo, Yi-Dong Lin, Patrick C.H. Hsieh, Erika I. H. Wei, Ying Chang Hsueh, Matthew L. Springer, Ming Long Yeh, Ming Jer Tang, Yu Ning Hu, Jieh Neng Wang, Min Yao Chang |
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Rok vydání: | 2012 |
Předmět: |
Vascular Endothelial Growth Factor A
Male medicine.medical_specialty Angiogenesis medicine.medical_treatment Genetic enhancement Myocardial Infarction Nanofibers Neovascularization Physiologic Bioengineering Revascularization Cardiovascular Regenerative Medicine Medical and Health Sciences Neovascularization chemistry.chemical_compound Medicine Animals Nanotechnology Physiologic Heart Disease - Coronary Heart Disease Tissue Engineering Tissue Scaffolds 5.2 Cellular and gene therapies business.industry Regeneration (biology) Myocardium General Medicine Biological Sciences Surgery Rats Vascular endothelial growth factor Heart Disease chemistry 5.1 Pharmaceuticals Cancer research Arteriogenesis medicine.symptom Development of treatments and therapeutic interventions business Myofibroblast Biotechnology |
Zdroj: | Science translational medicine, vol 4, iss 146 Lin, YD; Luo, CY; Hu, YN; Yeh, ML; Hsueh, YC; Chang, MY; et al.(2012). Instructive nanofiber scaffolds with VEGF create a microenvironment for arteriogenesis and cardiac repair. Science Translational Medicine, 4(146). doi: 10.1126/scitranslmed.3003841. UCSF: Retrieved from: http://www.escholarship.org/uc/item/094719gd |
DOI: | 10.1126/scitranslmed.3003841. |
Popis: | Angiogenic therapy is a promising approach for tissue repair and regeneration. However, recent clinical trials with protein delivery or gene therapy to promote angiogenesis have failed to provide therapeutic effects. A key factor for achieving effective revascularization is the durability of the microvasculature and the formation of new arterial vessels. Accordingly, we carried out experiments to test whether intramyocardial injection of self-assembling peptide nanofibers (NFs) combined with vascular endothelial growth factor (VEGF) could create an intramyocardial microenvironment with prolonged VEGF release to improve post-infarct neovascularization in rats. Our data showed that when injected with NF, VEGF delivery was sustained within the myocardium for up to 14 days, and the side effects of systemic edema and proteinuria were significantly reduced to the same level as that of control. NF/VEGF injection significantly improved angiogenesis, arteriogenesis, and cardiac performance 28 days after myocardial infarction. NF/VEGF injection not only allowed controlled local delivery but also transformed the injected site into a favorable microenvironment that recruited endogenous myofibroblasts and helped achieve effective revascularization. The engineered vascular niche further attracted a new population of cardiomyocyte-like cells to home to the injected sites, suggesting cardiomyocyte regeneration. Follow-up studies in pigs also revealed healing benefits consistent with observations in rats. In summary, this study demonstrates a new strategy for cardiovascular repair with potential for future clinical translation. |
Databáze: | OpenAIRE |
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