Delivery of Human Stromal Vascular Fraction Cells on Nanofibrillar Scaffolds for Treatment of Peripheral Arterial Disease

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.

Bioengineering Cell Therapy for Treatment of Peripheral Artery Disease

“…The recovery mechanisms underlying this therapeutic effect may include both angiogenesis and arteriogenesis, which could be mediated by patterned scaffold-induced activation of integrin-α1 and increased VEGF secretion. 54,63,64 These studies demonstrate an important role of nanopatterning cues in directing cell behavior, which can be applied toward improving the survival and angiogenic function of implanted cells in the setting of limb ischemia.…”

“…In vitro studies showed that SVF cells cultured on the scaffold had a 6-fold higher level of VEGF secretion, compared with that of SVF cells cultured in suspension. 63 Importantly, when SVF-seeded scaffolds were transplanted into immunodeficient mice with induced hind limb ischemia, the cell-seeded scaffolds induced a significant higher mean perfusion ratio after 14 days, compared with cells delivered in saline. 63 These findings show that both ECs and SVF cells delivered on aligned nanofibrillar scaffolds into ischemic tissue stimulated blood perfusion recovery.…”

“…63 Importantly, when SVF-seeded scaffolds were transplanted into immunodeficient mice with induced hind limb ischemia, the cell-seeded scaffolds induced a significant higher mean perfusion ratio after 14 days, compared with cells delivered in saline. 63 These findings show that both ECs and SVF cells delivered on aligned nanofibrillar scaffolds into ischemic tissue stimulated blood perfusion recovery. The recovery mechanisms underlying this therapeutic effect may include both angiogenesis and arteriogenesis, which could be mediated by patterned scaffold-induced activation of integrin-α1 and increased VEGF secretion.…”

Nanotechnology in interventional cardiology: A state-of-the-art review

“…6 ). Seeding of stromal vascular fraction nanomaterials enhances blood perfusion recovery in a mouse model of peripheral arterial disease [101] . Similarly, engineered vessel grafts show a promising alternative to autografts in coronary artery bypass surgery.…”

Microvascular fragment spheroids: Three-dimensional vascularization units for tissue engineering and regeneration

“… 11 Several studies already reported that SVF supports tissue revascularization along with the secretion of the angiogenic factors including vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF). 12 – 14 Recently, Muller et al 15 showed that SVF spheroids exhibit a high angiogenic potential and promote the formation of new blood vessels after in vivo transplantation.…”