Abstract
Current therapies for patients with critical limb ischemia have not reduced amputation risk owing to poor cell engraftment. The recombinant peptide Cellnest increases the engraftment rate of administered cells by forming a complex with the cells (CellSaic). We hypothesized that CellSaic containing adipose-derived stromal cells (ADSCs) could improve lower limb blood flow better than ADSCs alone, resulting in better transplanted cell engraftment. ADSCs were extracted from 8-week-old C57BL/6N mice. Thirty-two critical limb ischemia model mice were established by ligating femoral arteries. They were divided into CellSaic (n = 11), ADSC (n = 10), saline (n = 9), and Cellnest (n = 9) groups. Blood flow rate (affected side blood flow / healthy side blood flow × 100%) was evaluated using a laser Doppler blood flow meter every week. Mice were euthanized on day 28 for histological evaluation. Compared with the ADSC group (54.5 ± 17.2%), treated side blood flow rate of the CellSaic group (78.0 ± 24.9%) showed significant improvement on day 28 after administration (p < 0.05). CD31 staining showed significantly higher number of capillary vessels in the CellSaic group (53.0 ± 8.9 cells/mm3) than in the ADSC group (43.0 ± 6.8 cells/mm3) (p < 0.05). Fluorescent staining showed significantly higher number of arterioles containing both CD31 and αSMA double-positive cells in the CellSaic group than in the ADSC group (p < 0.05). CellSaic containing ADSCs exhibited superiority to ADSC transplantation alone in promoting functional angiogenesis, suggesting its potential in improving clinical outcomes of angiogenic therapy for ischemic limbs.
Highlights
30% patients with critical limb ischemia (CLI) lose their limbs, and approximately 25% die within 1 year despite several treatment options, such as surgical revascularization, percutaneous transluminal angioplasty, and drug therapy [1]
We hypothesized that compared with adipose-derived stromal cells (ADSCs) alone, CellSaic containing ADSCs improves lower limb blood flow
ADSCs extracted from C57BL/6N mice were positive for Sca-1 and CD44, which are markers for stromal cells, and RT-polymerase chain reaction (PCR) was performed on the 28th day after administration to evaluate vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) expression
Summary
30% patients with critical limb ischemia (CLI) lose their limbs, and approximately 25% die within 1 year despite several treatment options, such as surgical revascularization, percutaneous transluminal angioplasty, and drug therapy [1]. New angiogenesis therapies for CLI, such as gene and cell therapy, are expected to overcome. It has been reported that the recombinant peptide Cellnest increases the engraftment rate of administered cells by forming a complex with the cells, named CellSaic. Cellnest contains the cell adhesion RGD sequence of the human type I collagen α chain and can be used as a scaffold material for cells. CellSaic has been used to transplant pancreatic islet cells and has shown improvements in engraftment rate because of adequate intercellular spaces resulting in the migration of nutrient blood vessels [3]. We hypothesized that compared with adipose-derived stromal cells (ADSCs) alone, CellSaic containing ADSCs improves lower limb blood flow
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