Combined therapy for critical limb ischaemia: Biomimetic PLGA microcarriers potentiates the pro-angiogenic effect of adipose tissue stromal vascular fraction cells

Abstract

We propose a regenerative solution in the treatment of critical limb ischaemia (CLI). Poly-lactic/glycolic acid microcarriers were prepared and coated with laminin to be sterilized through γ-irradiation of 25 kGy at low temperature. Stromal vascular fraction (SVF) cells were extracted through enzymatic digestion of adipose tissue. Streptozotocin-induced diabetic mice underwent arteriotomy and received an administration of SVF cells combined or not with biomimetic microcarriers. Functional evaluation of the ischaemic limb was then reported, and tissue reperfusion was evaluated through fluorescence molecular tomography. Microcarriers were stable and functional after γ-irradiation until at least 12 months of storage. Mice that received an injection of SVF cells in the ischaemic limb have 22% of supplementary blood supply within this limb 7 days after surgery compared with vehicle, whereas no difference was observed at Day 14. With the combined therapy, the improvement of blood flow is significantly higher compared with vehicle, of about 31% at Day 7 and of about 11% at Day 14. Injection of SVF cells induces a significant 27% decrease of necrosis compared with vehicle. This effect is more important when SVF cells were mixed with biomimetic microcarriers: -37% compared with control. Although SVF cells injection leads to a non-significant 22% proprioception recovery, the combined therapy induces a significant recovery of about 27% compared with vehicle. We show that the combination of SVF cells from adipose tissue with laminin-coated poly-lactic/glycolic acid microcarriers is efficient for critical limb ischaemia therapy in a diabetic mouse model.

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

“…In our previous studies, we observed that nanofibrillar scaffolds had increased the survival duration of endothelial cells, and this potentially also applies to other cell types such as SVF cells ( Huang et al, 2013b ; Nakayama et al, 2015 ). It is plausible that the nanofibrillar scaffold prolonged the survival of SVF cells, resulting in a longer duration of therapeutic effect ( Hoareau et al, 2018 ). Besides VEGF, other interesting cellular signaling mechanisms may also be at play.…”

Surface Modification Progress for PLGA-Based Cell Scaffolds

“…In vivo experiments have demonstrated that a laminin-coated PLGA nerve catheter can not only promote the generation of sciatic nerve fibers [ 12 ], but it may also incorporate growth factors and adipogenic stem cells that promote the regeneration and functional recovery of the sciatic nerve [ 138 ]. In addition, Hoareau et al [ 139 ] used a laminin-coated PLGA microcarrier to deliver stromal vascular fraction (SVF) cells to the ischemic limb of a diabetic mouse model. The results showed that the delivering of cells via a microcarrier was more beneficial in terms of improving blood flow, reducing necrosis, and restoring limb sensation than injecting cells alone.…”