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The effect of autologous endothelial progenitor cell transplantation combined with extracorporeal shock-wave therapy on ischemic skin flaps in rats
Institution:1. Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People''s Hospital, Shanghai, China;2. Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People''s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;1. Centre de Recherche du CHU Ste-Justine, Université de Montréal, Montréal, Québec, Canada;2. Département de Pharmacologie, Université de Montréal, Montréal, Québec, Canada;3. Département de Somatologie, Université de Montréal, Montréal, Québec, Canada;1. Centre for Inflammatory Diseases, Monash University, Melbourne, Australia;2. Centre for Genetic Diseases, Monash Institute of Medical Research, Monash University, Melbourne, Australia;3. Department of Obstetrics & Gynaecology, University of Melbourne & Pregnancy Research Centre, Department of Perinatal Medicine, Royal Women''s Hospital, Melbourne, Australia;4. Gastroenterology and Hepatology Unit, Monash Health, Melbourne, Australia;5. Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia;1. Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia;2. Biochemistry Department, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia;1. Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy;2. Istituto Scienze dell''Alimentazione, CNR Avellino, Italy;3. Dipartimento di Bioscienze, Università di Parma, Italy (currently affiliated with Dipartimento di Biochimica e Biologia Molecolare, Università di Parma, Italy; Dipartimento di Medicina Occupazionale, Ergonomia e Disabilità, Laboratorio di Nanotecnologia, Fondazione IRCCS Salvatore Maugeri, Università di Pavia, Italy);4. Laboratorio di Nanotecnologia, Fondazione IRCCS Salvatore Maugeri, Università di Pavia, Italy (currently affiliated with Dipartimento di Medicina Occupazionale, Ergonomia e Disabilità, Laboratorio di Nanotecnologia, Fondazione IRCCS Salvatore Maugeri, Università di Pavia, Italy; Dipartimento di Medicina Molecolare, Centro di Ingegneria Tissutale, INSTM UdR Pavia, Università di Pavia, Italy);5. Servizio di Endoscopia Digestiva, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;6. Servizio di Immunogenetica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;7. Dipartimento di Onco-Ematologia Pediatrica e Medicina Trasfusionale, Ospedale Bambino Gesù, Roma e Università degli Studi di Pavia, Pavia, Italy;8. Servizio di Biometria e Statistica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;1. General Medical Center of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China;2. Department of Hematopoietic Stem Cell Transplantation, Hospital Affiliated with the Academy of Military Medical Sciences, Beijing, China;1. Centre for Clinical Brain Sciences, University of Edinburgh, Scotland;2. Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Scotland
Abstract:BackgroundEndothelial progenitor cells (EPCs) have been used to revascularize ischemic tissues, but only limited effect can be achieved. Extracorporeal shock-wave therapy (ESWT) is a promising angiogenic strategy. We hypothesized that EPC transplantation combined with ESWT would greatly benefit the survival of ischemic skin flaps.MethodsSixty-four male Sprague-Dawley rats were divided into 4 groups (n = 16 in each group): group 1 (serving as sham control), group 2 (treated with subcutaneous EPC implantation, 1.0 × 106 cells), group 3 (treated with ESWT, 300 impulses at 0.10 mJ/mm2) and group 4 (treated with EPCs implantation combined with ESWT). Ischemic skin flaps were made on the backs of rats and treated accordingly. Blood flow of skin flaps was measured periodically after operation, and flap survival rates were compared. Tissue samples were harvested at 2 weeks postoperatively from each group.ResultsThe survival rate of skin flaps in group 4 was 87.5 ± 10.23%, which was statistically significantly higher than other groups. Histologic examination showed that the capillary density was higher in the dual-treatment group than in the two single-treatment groups. Compared with groups 2 and 3, blood perfusion increased significantly in group 4. A drastic increase of vWF+ cells was observed in the ischemic skin flaps on immunofluorescence staining in group 4. The expressions of chemotactic factors and angiogenic factors were higher in group 4.ConclusionsCombined treatment with EPCs and ESWT is superior to either EPCs or ESWT alone in improving the survival of ischemic skin flaps in rats.
Keywords:angiogenic factors  apoptotic factors  chemotactic factors  endothelial progenitor cells  extracorporeal shock-wave therapy  ischemic skin flaps
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