{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:33:03Z","timestamp":1791592383278,"version":"4.3.4"},"reference-count":182,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Chronic limb-threatening ischemia (CLTI), the most advanced form of peripheral arterial disease (PAD), is the comorbidity primarily responsible for major lower-limb amputations, particularly for diabetic patients. Autologous cell therapy has been the focus of efforts over the past 20 years to create non-interventional therapeutic options for no-option CLTI to improve limb perfusion and wound healing. Among the different available techniques, peripheral blood mononuclear cells (PBMNC) appear to be the most promising autologous cell therapy due to physio-pathological considerations and clinical evidence, which will be discussed in this review. A meta-analysis of six clinical studies, including 256 diabetic patients treated with naive, fresh PBMNC produced via a selective filtration point-of-care device, was conducted. PBMNC was associated with a mean yearly amputation rate of 15.7%, a mean healing rate of 62%, and a time to healing of 208.6 \u00b1 136.5 days. Moreover, an increase in TcPO2 and a reduction in pain were observed. All-cause mortality, with a mean rate of 22.2% and a yearly mortality rate of 18.8%, was reported. No serious adverse events were reported. Finally, some practical and financial considerations are provided, which point to the therapy\u2019s recommendation as the first line of treatment for this particular and crucial patient group.<\/jats:p>","DOI":"10.3390\/jcm13237230","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T07:28:01Z","timestamp":1732778881000},"page":"7230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Immune-Centric Revolution Translated into Clinical Application: Peripheral Blood Mononuclear Cell (PBMNC) Therapy in Diabetic Patients with No-Option Critical Limb-Threatening Ischemia (NO-CLTI)\u2014Rationale and Meta-Analysis of Observational Studies"],"prefix":"10.3390","volume":"13","author":[{"given":"Laura","family":"Rehak","sequence":"first","affiliation":[{"name":"Athena Cell Therapy Technologies, 50126 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Giurato","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, Diabetes-Endocrine Section CTO Hospital, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9349-828X","authenticated-orcid":false,"given":"Matteo","family":"Monami","sequence":"additional","affiliation":[{"name":"Department of Diabetology Azienda Ospedaliera Universitaria Careggi, University of Florence, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3789-9622","authenticated-orcid":false,"given":"Marco","family":"Meloni","sequence":"additional","affiliation":[{"name":"Diabetic Foot Unit, Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3989-6484","authenticated-orcid":false,"given":"Alessia","family":"Scatena","sequence":"additional","affiliation":[{"name":"Diabetology Unit, San Donato Hospital Arezzo, Local Health Authorities Southeast Tuscany, 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0074-2357","authenticated-orcid":false,"given":"Andrea","family":"Panunzi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, Diabetes-Endocrine Section CTO Hospital, Tor Vergata University of Rome, 00133 Rome, Italy"},{"name":"PhD School of Applied Medical and Surgical Sciences, University of Rome Tor Vergata Italy, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada Maria","family":"Manti","sequence":"additional","affiliation":[{"name":"Athena Cell Therapy Technologies, 50126 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Maria Ferdinando","family":"Caravaggi","sequence":"additional","affiliation":[{"name":"Diabetic Foot Unit, IRCCS MultiMedica Milan, 20099 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-2091","authenticated-orcid":false,"given":"Luigi","family":"Uccioli","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, Diabetes-Endocrine Section CTO Hospital, Tor Vergata University of Rome, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2020). 10. 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