{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:20Z","timestamp":1787028440728,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 106-2314-B-182A-108 -MY3"],"award-info":[{"award-number":["MOST 106-2314-B-182A-108 -MY3"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study tested whether circulatory endothelial progenitor cells (EPCs) derived from peripheral arterial occlusive disease (PAOD) patients after receiving combined autologous CD34+ cell and hyperbaric oxygen (HBO) therapy (defined as rejuvenated EPCs) would salvage nude mouse limbs against critical limb ischemia (CLI). Adult-male nude mice (n = 40) were equally categorized into group 1 (sham-operated control), group 2 (CLI), group 3 (CLI-EPCs (6 \u00d7 105) derived from PAOD patient\u2019s circulatory blood prior to CD34+ cell and HBO treatment (EPCPr-T) by intramuscular injection at 3 h after CLI induction) and group 4 (CLI-EPCs (6 \u00d7 105) derived from PAOD patient\u2019s circulatory blood after CD34+ cell and HBO treatment (EPCAf-T) by the identical injection method). By 2, 7 and 14 days after the CLI procedure, the ischemic to normal blood flow (INBF) ratio was highest in group 1, lowest in group 2 and significantly lower in group 4 than in group 3 (p &lt; 0.0001). The protein levels of endothelial functional integrity (CD31\/von Willebrand factor (vWF)\/endothelial nitric-oxide synthase (eNOS)) expressed a similar pattern to that of INBF. In contrast, apoptotic\/mitochondrial-damaged (mitochondrial-Bax\/caspase-3\/PARP\/cytosolic-cytochrome-C) biomarkers and fibrosis (Smad3\/TGF-\u00df) exhibited an opposite pattern, whereas the protein expressions of anti-fibrosis (Smad1\/5 and BMP-2) and mitochondrial integrity (mitochondrial-cytochrome-C) showed an identical pattern of INBF (all p &lt; 0.0001). The protein expressions of angiogenesis biomarkers (VEGF\/SDF-1\u03b1\/HIF-1\u03b1) were progressively increased from groups 1 to 3 (all p &lt; 0.0010). The number of small vessels and endothelial cell surface markers (CD31+\/vWF+) in the CLI area displayed an identical pattern of INBF (all p &lt; 0.0001). CLI automatic amputation was higher in group 2 than in other groups (all p &lt; 0.001). In conclusion, EPCs from HBO-C34+ cell therapy significantly restored the blood flow and salvaged the CLI in nude mice.<\/jats:p>","DOI":"10.3390\/ijms21217887","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T02:34:54Z","timestamp":1603679694000},"page":"7887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Circulatory Rejuvenated EPCs Derived from PAOD Patients Treated by CD34+ Cells and Hyperbaric Oxygen Therapy Salvaged the Nude Mouse Limb against Critical Ischemia"],"prefix":"10.3390","volume":"21","author":[{"given":"Yin-Chia","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiunn-Jye","family":"Sheu","sequence":"additional","affiliation":[{"name":"Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8719-4017","authenticated-orcid":false,"given":"John Y.","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Lin","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Nursing, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Cheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"},{"name":"Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung 80756, Taiwan"},{"name":"Post-Baccalaureate Program in Nursing, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1989-9752","authenticated-orcid":false,"given":"Pei-Hsun","family":"Sung","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2335-0172","authenticated-orcid":false,"given":"Yi-Chen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Hung","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2527-2825","authenticated-orcid":false,"given":"Kuan-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-5717","authenticated-orcid":false,"given":"Hon-Kan","family":"Yip","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Department of Nursing, Asia University, Taichung 41354, Taiwan"},{"name":"Department of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, Xiamen Chang Gung Hospital, Xiamen 361028, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1056\/NEJM200105243442108","article-title":"Medical Treatment of Peripheral Arterial Disease and Claudication","volume":"344","author":"Hiatt","year":"2001","journal-title":"N. 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