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Local delivery of cardiac stem cells overexpressing HIF-1α promotes angiogenesis and muscular tissue repair in a hind limb ischemia model
- Source :
- Journal of controlled release : official journal of the Controlled Release Society. 322
- Publication Year :
- 2019
-
Abstract
- Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease, associated with significant risk of limb loss, morbidity and mortality; however, there remains unmet therapeutic needs for arterial revascularization and ischemic tissue repair. Stem cell therapies have emerged as compelling candidates due to beneficial proangiogenic and immunosuppressive function. Nevertheless, in vivo efficacy was insufficient in proliferation, differentiation and survival/engraftment rate. Cardiac stem cells (CSCs) was firstly attempted for CLI as a novel therapeutic modality to provide superior angiogenic potency to bone marrow-derived stem cells (BMSCs). It was noted that CSCs demonstrated 3.2-fold in HGF, 2.9-fold in VEGF and 8.7-fold in PDGF-B higher gene expressions compared to BMSCs. To enhance the hypoxia-induced proangiogenic effect, CSCs were transfected with hypoxia-inducible factor-1 alpha (HIF-1α) by using electroporation method, specifically optimized for CSCs yielding 45.77% of transfection efficiency and 89.75% of viability. HIF-1α overexpression significantly increased CSC survival in hypoxia, proangiogenic factors production and endothelial differentiation. In mouse hind limb ischemia model, local intramuscular delivery of CSC overexpressing HIF-1α (HIF-CSC) significantly improved the blood flow recovery. Histological analysis revealed that muscle degeneration and fibrosis in the ischemic limb were attenuated. Local delivery of HIF-CSC might be a promising option for ischemic tissue restoration.
- Subjects :
- Angiogenesis
Pharmaceutical Science
Neovascularization, Physiologic
02 engineering and technology
03 medical and health sciences
Mice
Peripheral Arterial Disease
Fibrosis
Ischemia
medicine
Animals
Therapeutic angiogenesis
030304 developmental biology
0303 health sciences
biology
Neovascularization, Pathologic
business.industry
Cell Differentiation
Mesenchymal Stem Cells
Critical limb ischemia
Transfection
Hypoxia (medical)
021001 nanoscience & nanotechnology
medicine.disease
Hypoxia-Inducible Factor 1, alpha Subunit
Cancer research
biology.protein
Stem cell
medicine.symptom
0210 nano-technology
business
Platelet-derived growth factor receptor
Subjects
Details
- ISSN :
- 18734995
- Volume :
- 322
- Database :
- OpenAIRE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Accession number :
- edsair.doi.dedup.....210242d00d5aff6ed450c6661050921b