Abstract
Cell therapy for treatment of peripheral arterial disease (PAD) is a promising approach but is limited by poor cell survival when cells are delivered using saline. The objective of this study was to examine the feasibility of aligned nanofibrillar scaffolds as a vehicle for the delivery of human stromal vascular fraction (SVF), and then to assess the efficacy of the cell-seeded scaffolds in a murine model of PAD. Flow cytometric analysis was performed to characterize the phenotype of SVF cells from freshly isolated lipoaspirate, as well as after attachment onto aligned nanofibrillar scaffolds. Flow cytometry results demonstrated that the SVF consisted of 33.1 ± 9.6% CD45+ cells, a small fraction of CD45–/CD31+ (4.5 ± 3.1%) and 45.4 ± 20.0% of CD45–/CD31–/CD34+ cells. Although the subpopulations of SVF did not change significantly after attachment to the aligned nanofibrillar scaffolds, protein secretion of vascular endothelial growth factor (VEGF) significantly increased by six-fold, compared to SVF cultured in suspension. Importantly, when SVF-seeded scaffolds were transplanted into immunodeficient mice with induced hindlimb ischemia, the cell-seeded scaffolds induced a significant higher mean perfusion ratio after 14 days, compared to cells delivered using saline. Together, these results show that aligned nanofibrillar scaffolds promoted cellular attachment, enhanced the secretion of VEGF from attached SVF cells, and their implantation with attached SVF cells stimulated blood perfusion recovery. These findings have important therapeutic implications for the treatment of PAD using SVF.
Highlights
Peripheral arterial disease (PAD) affects over 10 million people in the United States (Benjamin et al, 2018)
We show that the subpopulation of stromal vascular fraction (SVF) cells that adhered to the nanofibrillar scaffold had significantly higher release of vascular endothelial growth factor (VEGF), but without a significant change in the CD45−/CD31−/ CD34+ cell fraction, compared to bulk SVF cells in suspension
When implanted into mice with induced hindlimb ischemia as an experimental model of PAD, the SVF-seeded scaffolds significantly increased blood perfusion, compared to cell delivery in saline. These findings suggest that aligned nanofibrillar scaffolds promoted the adhesion of SVF cells that induce angiogenesis and blood perfusion recovery, which has important therapeutic implications for the treatment of PAD
Summary
Peripheral arterial disease (PAD) affects over 10 million people in the United States (Benjamin et al, 2018). It is associated with reduced blood flow to the arms and legs, leading to pain and even limb amputation. Severe cases of PAD lead to critical limb ischemia (CLI) that is characterized by rest pain, gangrene formation, Stromal Vascular Fraction on Aligned Scaffold and possible amputation of the limb (Davies, 2012). Current clinical treatments of PAD involve surgical interventions including bypass grafting and angioplasty to restore blood flow to the affected limb. A large portion of patients with severe disease lack suitable vessels for vascular intervention (Gerhard et al, 1995). There is an urgent need for alternative approaches to stimulate angiogenesis
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