Hyperbaric oxygen facilitates the effect of endothelial progenitor cell therapy on improving outcome of rat critical limb ischemia

American Journal of Translational Research

Shan-Ling Hsu¹  Kuan-Hung Chen²  Chien-Chang Chen³  Pei-Hsun Sung⁴  Pao-Yuan Lin⁵  Pei-Lin Shao⁶  Re-Wen Wu⁷  Sheng-Ying Chung⁸  Jiunn-Jye Sheu⁹  Tsung-Cheng Yin^1,10 

[1] Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Department of Hyperbaric Oxygen Therapy Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 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;Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan;Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan

关键词: Critical limb ischemia;    hyperbaric oxygen;    endothelial progenitor cells;    angiogenesis;    apoptosis;    fibrosis;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

We tested the hypothesis that hyperbaric oxygen (HBO) (100% oxygen/2.4 atmospheres) facilitated the effect of autologous endothelial progenitor cell (EPC) therapy on restoring the blood flow in rat critical-limb ischemia (CLI). Adult-male-SD rats (n = 8/each group) were categorized into group 1 [sham control (SC)], group 2 (CLI-treated with culture medium), group 3 [CLI-intermittent HBO (3 h/day for 5 consecutive days after CLI), group 4 (CLI-EPC/2.0 × 106 cells), and group 5 (CLI-HBO-EPC). By day 5 after CLI, flow cytometry showed that the circulating EPC (Sca-1/CD31+/C-kit/CD31+/CD34+) levels were highest in group 5 and lowest in group 2 (all P < 0.001). By day 14, laser Doppler demonstrated that the ratio of blood flow (i.e., CLI to normal hind-limb) was highest in group 1, lowest in group 2 and significantly higher in group 5 than in groups 3 and 4 (all P < 0.0001). The protein expressions of endothelial-cell biomarkers (CD31/vWF/eNOS), and numbers of endothelial-cell markers (CD31+/vWF+) and small vessels exhibited a similar pattern to blood-flow ratio among five groups, whereas the angiogenesis parameters in protein (CXCR4/SDF-1α/HIF-1α/VEGF) and cellular (HIF-1α/SDF-1α/CXCR4+) levels were progressively increased from groups 1 to 5 (all P < 0.0001). The protein expression of apoptotic (mitochondrial-Bax/cleaved-capspase-3/PARP), fibrotic (p-Smad3/TGF-ß) and mitochondrial-damaged (cytosolic-cytochrome C) exhibited an opposite pattern, whereas the protein expressions of anti-fibrotic (BMP-2/p-Smad1/5) and mitochondrial integrity (mitochondrial-cytochrome C) exhibited an identical pattern of ratio of blood flow among the five groups (all P < 0.0001). Combined HBO-EPC therapy is superior to either one alone in improving ischemia in rodent CLI.

【 授权许可】

CC BY-NC