Extracorporeal shock wave-assisted adipose-derived fresh stromal vascular fraction restores the blood flow of critical limb ischemia in rat.

Vascul Pharmacol

Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan; Department of Nursing, Asia University, Taichung 41354, Taiwan. Electronic address:

Published: February 2019

We tested the hypothesis that extracorporeal-shock-wave (ECSW)-assisted adipose-derived stromal vascular fraction (SVF) therapy was better than either one for restoring the blood flow in critical limb ischemia (CLI). Adult male-SD rats were categorized into group 1 (sham-operated-control), group 2 (CLI), group 3 [CLI + ECSW (280 impulses/0.10 mJ/mm) applied to left inguinal area at 3 h after CLI], group 4 [CLI + SVF (1.2 × 10) implanted into CLI area at 3 h after CLI], group 5 (CLI + ECSW-SVF). In vitro studies showed that ECSW significantly enhanced angiogenesis in human umbilical-vein endothelial cells and carotid-artery ring, and SVF significantly suppressed inflammation (TNF-α/NF-Κb/IL-1ß/MMP-9) in smooth-muscle cells treated by LPS (all p < .001). By day 14 after CLI, the ratio of ischemic/normal blood flow (INBF) was highest in group 1, lowest in group 2, significantly higher in group 5 than in groups 3 and 4, but no difference was shown between the latter two groups (all p < .001). The fibrotic area in CLI region exhibited an opposite pattern of INBF ratio (all p < .0001). Protein (CD31/vWF/eNOS) and cellular (CD31/vWF) expressions and number of small vessels in CLI area exhibited an identical pattern, whilst protein expressions of apoptotic (caspase3/PARP/mitochondrial-Bax) fibrotic/DNA-damaged (Samd3/TFG-ß/γ-H2AX) biomarkers exhibited an opposite pattern to INBF among five groups (all p < .0001). The numbers of angiogenetic cells in CLI region (SDF-1α/VEGF/CXCR4) and endothelial-progenitor cells (C-kit/CD31+//Sca-1/CD31+//CD34/KDR+/VE-cadherin/CD34+) in circulation significantly and progressively increased from groups 2 to 5 (all p < .0001). In conclusion, ECSW-SVF therapy effectively enhanced angiogenesis and restoration of blood flow in CLI area.

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http://dx.doi.org/10.1016/j.vph.2018.12.003DOI Listing

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