{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:15:59Z","timestamp":1773285359301,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":1226,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Critical limb ischemia (CLI) is a devastating disease in patients undergoing hemodialysis (HD). Based on the unsatisfactory results of autologous mononuclear cell transplantation for patients with CLI undergoing HD, we conducted a phase II clinical trial to evaluate the safety and efficacy of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood-derived autologous purified CD34 positive (CD34+) cell transplantation for CLI in patients undergoing HD. Six patients with CLI (two with Rutherford category 4 and four with Rutherford category 5) were enrolled. As for primary endpoint, there were no major adverse events related to this therapy. As for efficacy, the amputation-free survival rate was 100% at 1 year after cell therapy. Both rest pain scale and ulcer size were significantly improved as early as 4 weeks after therapy compared with baseline (p &amp;lt; .01), and three out of five ulcers completely healed within 12 weeks after cell transplantation. Clinical severity, including Fontaine scale and Rutherford category, significantly improved at 24 weeks after cell transplantation (p &amp;lt; .05), and further improved at 52 weeks (p &amp;lt; .01) compared with baseline. The improvement rate from CLI stage to non-CLI stage was 83.3% at 52 weeks. Toe skin perfusion pressure and absolute claudication distance were also significantly improved. In conclusion, G-CSF-mobilized peripheral blood CD34+ cell transplantation was safe, feasible, and effective for patients with CLI undergoing HD.<\/jats:p>","DOI":"10.1002\/sctm.18-0104","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T13:21:43Z","timestamp":1532956903000},"page":"774-782","source":"Crossref","is-referenced-by-count":22,"title":["Autologous Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood CD34 Positive Cell Transplantation for Hemodialysis Patients with Critical Limb Ischemia: A Prospective Phase II Clinical Trial"],"prefix":"10.1093","volume":"7","author":[{"given":"Takayasu","family":"Ohtake","sequence":"first","affiliation":[{"name":"a Department of Kidney Disease and Transplant Center Shonan Kamakura General Hospital, Kamakura, Japan"},{"name":"b Division of Regenerative Medicine, Department of Center for Clinical and Translational Science Shonan Kamakura General Hospital, Kamakura, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Mochida","sequence":"additional","affiliation":[{"name":"a Department of Kidney Disease and Transplant Center Shonan Kamakura General Hospital, Kamakura, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunihiro","family":"Ishioka","sequence":"additional","affiliation":[{"name":"a Department of Kidney Disease and Transplant Center Shonan Kamakura General Hospital, Kamakura, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Machiko","family":"Oka","sequence":"additional","affiliation":[{"name":"a Department of Kidney Disease and Transplant Center Shonan Kamakura General Hospital, Kamakura, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Maesato","sequence":"additional","affiliation":[{"name":"a Department of Kidney Disease and Transplant Center Shonan Kamakura General Hospital, Kamakura, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidekazu","family":"Moriya","sequence":"additional","affiliation":[{"name":"a Department of Kidney Disease and Transplant Center Shonan Kamakura General Hospital, Kamakura, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumi","family":"Hidaka","sequence":"additional","affiliation":[{"name":"a Department of Kidney Disease and Transplant Center Shonan Kamakura General Hospital, Kamakura, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Higashide","sequence":"additional","affiliation":[{"name":"c Translational Research Informatics Center Foundation for Biomedical Research and Innovation, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Ioji","sequence":"additional","affiliation":[{"name":"c Translational Research Informatics Center Foundation for Biomedical Research and Innovation, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Fujita","sequence":"additional","affiliation":[{"name":"c Translational Research Informatics Center Foundation for Biomedical Research and Innovation, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsuhiko","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"c Translational Research Informatics Center Foundation for Biomedical Research and Innovation, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Fukushima","sequence":"additional","affiliation":[{"name":"c Translational Research Informatics Center Foundation for Biomedical Research and Innovation, Kobe, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuzo","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"a Department of Kidney Disease and Transplant Center Shonan Kamakura General Hospital, Kamakura, Japan"},{"name":"b Division of Regenerative Medicine, Department of Center for Clinical and Translational Science Shonan Kamakura General Hospital, Kamakura, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,7,30]]},"reference":[{"key":"2022022809002149500_sct312342-bib-0001","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.jvs.2013.05.027","article-title":"The prognosis of patients on hemodialysis with foot lesion","volume":"58","author":"Orimoto","year":"2013","journal-title":"J Vasc Surg"},{"key":"2022022809002149500_sct312342-bib-0002","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1093\/ndt\/gfr760","article-title":"Peripheral vascular disease severity impacts health outcomes and health-related quality of life in maintenance hemodialysis patients in the HEMO study","volume":"27","author":"Liu","year":"2012","journal-title":"Nephrol Dial Transplant"},{"key":"2022022809002149500_sct312342-bib-0003","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jvs.2010.09.070","article-title":"Lower limbs\u2019 arterial calcification on the prevalence and severity of PAD in patients on hemodialysis","volume":"53","author":"Ohtake","year":"2011","journal-title":"J Vasc Surg"},{"key":"2022022809002149500_sct312342-bib-0004","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.ejvs.2012.07.017","article-title":"Angiographic restenosis and its clinical impact after infrapopliteal angioplasty","volume":"44","author":"Iida","year":"2012","journal-title":"Eur J Vasc Endovasc Surg"},{"key":"2022022809002149500_sct312342-bib-0005","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/ccd.25676","article-title":"Three-year clinical outcome after inftapopliteal angioplasty for critical limb ischemia in hemodialysis patients with minor or major tissue loss","volume":"86","author":"Nakano","year":"2015","journal-title":"Catheter Cardiovasc Interv"},{"key":"2022022809002149500_sct312342-bib-0006","doi-asserted-by":"crossref","first-page":"404","DOI":"10.5551\/jat.25056","article-title":"Prognostic factors in hemodialysis patients undergoing endovascular treatment for critical limb ischemia due to isolated below-knee disease","volume":"22","author":"Suematsu","year":"2015","journal-title":"Atheroscler Thromb"},{"key":"2022022809002149500_sct312342-bib-0007","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ejvs.2014.08.022","article-title":"Clinical outcomes after infrainguinal bypass grafting for critical limb ischemia in patients with dialysis-dependent end-stage renal failure","volume":"48","author":"Kodama","year":"2014","journal-title":"Eur J Vasc Endovasc Surg"},{"key":"2022022809002149500_sct312342-bib-0008","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jvs.2014.09.007","article-title":"Clinical outcome after infrapopliteal bypass surgery in chronic hemodialysis patients with critical limb ischemia","volume":"61","author":"Kumada","year":"2015","journal-title":"J Vasc Surg"},{"key":"2022022809002149500_sct312342-bib-0009","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1126\/science.275.5302.964","article-title":"Isolation of putative progenitor endothelial cells for angiogenesis","volume":"275","author":"Asahara","year":"1997","journal-title":"Science"},{"key":"2022022809002149500_sct312342-bib-0010","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0140-6736(02)09670-8","article-title":"Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone marrow cells: A pilot study and a randomized controlled trial","volume":"360","author":"Tateishi-Yuyama","year":"2002","journal-title":"Lancet"},{"key":"2022022809002149500_sct312342-bib-0011","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.2337\/diacare.28.9.2155","article-title":"Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes","volume":"28","author":"Huang","year":"2005","journal-title":"Diabetes Care"},{"key":"2022022809002149500_sct312342-bib-0012","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1253\/circj.71.196","article-title":"Safety and efficacy of autologous progenitor cell transplantation for therapeutic angiogenesis in patients with critical limb ischemia","volume":"71","author":"Kajiguchi","year":"2007","journal-title":"Circ J"},{"key":"2022022809002149500_sct312342-bib-0013","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.ahj.2008.06.025","article-title":"Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic angiogenesis by cell transplantation [TACT] trial)","volume":"156","author":"Matoba","year":"2008","journal-title":"Am heart J"},{"key":"2022022809002149500_sct312342-bib-0014","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1002\/stem.207","article-title":"Intramuscular transplantation of G-CSF-mobilized CD34+ cells in patients with critical limb ischemia: A phase I\/IIa, multicenter, single-blinded, dose-escalation clinical trial","volume":"27","author":"Kawamoto","year":"2009","journal-title":"Stem Cells"},{"key":"2022022809002149500_sct312342-bib-0015","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.atherosclerosis.2009.07.050","article-title":"Long-term clinical outcomes for patients with lower limb ischemia implanted with G-CSF-mobilized autologous peripheral blood mononuclear cells","volume":"208","author":"Horie","year":"2010","journal-title":"Atherosclerosis"},{"key":"2022022809002149500_sct312342-bib-0016","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1161\/CIRCINTERVENTIONS.108.799361","article-title":"Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia","volume":"2","author":"Moriya","year":"2009","journal-title":"Circ Cardiovasc Intervent"},{"key":"2022022809002149500_sct312342-bib-0017","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/bmt.2010.110","article-title":"Bone marrow mononuclear cells versus G-CSF-mobilized peripheral blood mononuclear cells for treatment of lower limb ASO: Pooled analysis for long-term prognosis","volume":"46","author":"Onodera","year":"2011","journal-title":"Bone Marrow Transplant"},{"key":"2022022809002149500_sct312342-bib-0018","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1161\/CIRCINTERVENTIONS.112.968321","article-title":"A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia","volume":"5","author":"Losordo","year":"2012","journal-title":"Circ Cardiovasc Interv"},{"key":"2022022809002149500_sct312342-bib-0019","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jvs.2013.01.037","article-title":"Transplantation of purified CD34+ cells in the treatment of critical limb ischemia","volume":"58","author":"Dong","year":"2013","journal-title":"J Vasc Surg"},{"key":"2022022809002149500_sct312342-bib-0020","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/1479-5876-11-143","article-title":"A double blind randomized placebo controlled phase I\/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia","volume":"11","author":"Gupta","year":"2013","journal-title":"J Transl Med"},{"key":"2022022809002149500_sct312342-bib-0021","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1253\/circj.CJ-13-0864","article-title":"Phase II clinical trial of CD34+ cell therapy to explore endpoint selection and timing in patients with critical limb ischemia","volume":"78","author":"Fujita","year":"2014","journal-title":"Circ J"},{"key":"2022022809002149500_sct312342-bib-0022","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3727\/096368912X658007","article-title":"Autologous G-CSF-mobilized peripheral blood CD34+ cell therapy for diabetic patients with chronic nonhealing ulcer","volume":"23","author":"Tanaka","year":"2014","journal-title":"Cell Transplant"},{"key":"2022022809002149500_sct312342-bib-0023","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1182\/blood.V97.10.3075","article-title":"Numerous growth factors, cytokines, and chemokines are secreted by human CD34(+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine\/paracrine manner","volume":"97","author":"Majka","year":"2001","journal-title":"Blood"},{"key":"2022022809002149500_sct312342-bib-0024","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1161\/CIRCRESAHA.111.253286","article-title":"Exosomes from human CD34+ stem cells mediate their proangiogenic paracrine activity","volume":"109","author":"Sahoo","year":"2011","journal-title":"Circ Res"},{"key":"2022022809002149500_sct312342-bib-0025","first-page":"873","article-title":"Clinical management of diabetic retinopathy","volume":"93","author":"Fukuda","year":"1989","journal-title":"Nippon Ganka Gakkai Zasshi"},{"key":"2022022809002149500_sct312342-bib-0026","first-page":"81","article-title":"Inter-society consensus for the management of peripheral arterial disease","volume":"26","author":"Norgren","year":"2007","journal-title":"Int Angiol"},{"key":"2022022809002149500_sct312342-bib-0027","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s00277-013-1760-y","article-title":"The effect of diabetes mellitus and end-stage renal disease on the number of CD34+ cells in the blood","volume":"92","author":"Pala","year":"2013","journal-title":"Ann Hematol"},{"key":"2022022809002149500_sct312342-bib-0028","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1111\/j.1538-7836.2009.03540.x","article-title":"Levels of circulating endothelial progenitor cells are related to uremic toxins and vascular injury in hemodialysis patients","volume":"7","author":"Jourde-Chiche","year":"2009","journal-title":"J Thromb Haematol"},{"key":"2022022809002149500_sct312342-bib-0029","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1038\/ki.2008.495","article-title":"Low circulating CD34+ cell count is associated with poor prognosis in chronic hemodialysis patients","volume":"74","author":"Maruyama","year":"2008","journal-title":"Kidney Int"},{"key":"2022022809002149500_sct312342-bib-0030","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000430471","article-title":"Circulating endothelial progenitor cell levels predict cardiovascular events in end-stage renal disease patients on maintenance hemodialysis","volume":"130","author":"Lee","year":"2015","journal-title":"Nephron"},{"key":"2022022809002149500_sct312342-bib-0031","doi-asserted-by":"crossref","first-page":"e55592","DOI":"10.1371\/journal.pone.0055592","article-title":"Bone marrow alterations and lower endothelial progenitor cell numbers in critical limb ischemia patients","volume":"8","author":"Teraa","year":"2013","journal-title":"PLoS One"},{"key":"2022022809002149500_sct312342-bib-0032","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1046\/j.1365-201x.2000.00640.x","article-title":"Plasma from ESRD patients inhibits nitric oxide synthase activity in cultured human and bovine endothelial cells","volume":"168","author":"Xiao","year":"2000","journal-title":"Acta Physiol Scand"},{"key":"2022022809002149500_sct312342-bib-0033","doi-asserted-by":"crossref","first-page":"H1378","DOI":"10.1152\/ajpheart.00888.2005","article-title":"Stem cell mobilization by hyperbaric oxygen","volume":"290","author":"Thom","year":"2006","journal-title":"Am J Physiol Circ Physiol"},{"key":"2022022809002149500_sct312342-bib-0034","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1161\/CIRCULATIONAHA.106.644518","article-title":"CD34-positive cell exhibit increased potency and safety for therapeutic neovascularization after myocardial infarction compared with total mononuclear cells","volume":"114","author":"Kawamoto","year":"2006","journal-title":"Circulation"},{"key":"2022022809002149500_sct312342-bib-0035","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/j.1542-4758.2009.00371.x","article-title":"Increased leukocyte aggregations are associated with atherosclerosis in patients with hemodialysis","volume":"13","author":"Kobayashi","year":"2009","journal-title":"Hemodial Int"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fsctm.18-0104","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/7\/11\/774\/42625250\/stcltm_7_11_774.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/7\/11\/774\/42625250\/stcltm_7_11_774.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T09:03:27Z","timestamp":1646039007000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/7\/11\/774\/6449290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,30]]},"references-count":35,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,7,30]]},"published-print":{"date-parts":[[2018,11,1]]}},"URL":"https:\/\/doi.org\/10.1002\/sctm.18-0104","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2018,11,1]]},"published":{"date-parts":[[2018,7,30]]}}}