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
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