{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:15:54Z","timestamp":1790914554586,"version":"4.1.0"},"reference-count":80,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>When in critical limb ischemia (CLI) the healing process aborts or does not follow an orderly and timely sequence, a chronic vascular wound develops. The latter is major problem today, as their epidemiology is continuously increasing due to the aging population and a growth in the incidence of the underlying diseases. In the US, the mean annualized prevalence of necrotic wounds due to the fact of CLI is 1.33% (95% CI, 1.32\u20131.34%), and the cost of dressings alone has been estimated at USD 5 billion per year from healthcare budgets. A promising cell treatment in wound healing is the local injection of peripheral blood mononuclear cells (PBMNCs). The treatment is aimed to induce angiogenesis as well to switch inflammatory macrophages, called the M1 phenotype, into anti-inflammatory macrophages, called M2, a phenotype devoted to tissue repair. This mechanism is called polarization and is a critical step for the healing of all human tissues. Regarding the clinical efficacy of PBMNCs, the level of evidence is still low, and a considerable effort is necessary for completing the translational process toward the patient bed site. From this point of view, it is crucial to identify some candidate biomarkers to detect the switching process from M1 to M2 in response to the cell treatment.<\/jats:p>","DOI":"10.3390\/diagnostics12051137","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T08:21:25Z","timestamp":1651652485000},"page":"1137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PBMNCs Treatment in Critical Limb Ischemia and Candidate Biomarkers of Efficacy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6750-919X","authenticated-orcid":false,"given":"Matilde","family":"Zamboni","sequence":"first","affiliation":[{"name":"Unit of Vascular and Endovascular Surgery, San Martino Hospital, 32100 Belluno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Pedriali","sequence":"additional","affiliation":[{"name":"Unit of Surgical Pathology, Azienda Ospedaliera-Universitaria, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2848-7127","authenticated-orcid":false,"given":"Luca","family":"Ferretto","sequence":"additional","affiliation":[{"name":"Unit of Vascular and Endovascular Surgery, San Martino Hospital, 32100 Belluno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Scian","sequence":"additional","affiliation":[{"name":"Unit of Vascular and Endovascular Surgery, Azienda Ospedaliera-Universitaria, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ghirardini","sequence":"additional","affiliation":[{"name":"Unit of Vascular and Endovascular Surgery, San Martino Hospital, 32100 Belluno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bozza","sequence":"additional","affiliation":[{"name":"Unit of Vascular and Endovascular Surgery, San Martino Hospital, 32100 Belluno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romeo","family":"Martini","sequence":"additional","affiliation":[{"name":"Unit of Vascular and Endovascular Surgery, San Martino Hospital, 32100 Belluno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Irsara","sequence":"additional","affiliation":[{"name":"Unit of Vascular and Endovascular Surgery, San Martino Hospital, 32100 Belluno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.atherosclerosis.2018.05.033","article-title":"Update on peripheral artery disease: Epidemiology and evidence-based facts","volume":"275","author":"Shu","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_2","first-page":"499","article-title":"Surgical Treatment of Peripheral Circulation Disorders","volume":"21","author":"Fontaine","year":"1954","journal-title":"Helv. Chir. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0741-5214(97)70045-4","article-title":"Recommended standards for reports dealing with lower extremity ischemia: Revised version","volume":"26","author":"Rutherford","year":"1997","journal-title":"J. Vasc. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/S0140-6736(13)61249-0","article-title":"Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis","volume":"382","author":"Fowkes","year":"2013","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.jvs.2014.03.290","article-title":"Epidemiology of peripheral arterial disease and critical limb ischemia in an insured national population","volume":"60","author":"Nehler","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3S","DOI":"10.1016\/j.jvs.2019.02.016","article-title":"Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia","volume":"69","author":"Conte","year":"2019","journal-title":"J. Vasc. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jvs.2013.08.003","article-title":"Society for Vascular Surgery Lower Extremity Guidelines Committee. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on wound, ischemia, and foot infection (WIfI)","volume":"59","author":"Mills","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1177\/0003319720976823","article-title":"Evolution of Major Amputation Risk in Patients Hospitalized in France for Critical Limb Ischemia: The COPART Registry","volume":"72","author":"Coudene","year":"2021","journal-title":"Angiology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jakubiak, G.K., Pawlas, N., Cie\u015blar, G., and Stanek, A. (2021). Pathogenesis and Clinical Significance of In-Stent Restenosis in Patients with Diabetes. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph182211970"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"402","DOI":"10.23736\/S0021-9509.17.09844-5","article-title":"Surgical and endovascular venous arterialization: Ready to take the \u201cdesert\u201d by storm?","volume":"58","author":"Schreve","year":"2017","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.ejvs.2014.07.001","article-title":"The effect of diabetes mellitus on costs and length of stay in patients with peripheral arterial disease undergoing vascular surgery","volume":"48","author":"Malone","year":"2014","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_12","first-page":"e009724","article-title":"The cost of critical limb ischemia (CLI). Why is the disease so costly?","volume":"7","author":"Yost","year":"2019","journal-title":"Sage Group"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e875","DOI":"10.1161\/CIR.0000000000000967","article-title":"Reducing Nontraumatic Lower-Extremity Amputations by 20% by 2030: Time to Get to Our Feet: A Policy Statement from the American Heart Association","volume":"143","author":"Creager","year":"2021","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.15283\/ijsc20088","article-title":"Autologous Bone-Marrow vs. Peripheral Blood Mononuclear Cells Therapy for Peripheral Artery Disease in Diabetic Patients","volume":"14","author":"Yunir","year":"2021","journal-title":"Int. J. Stem Cells"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s00395-011-0224-6","article-title":"Secretome of apoptotic peripheral blood cells (APOSEC) confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: A preclinical study","volume":"106","author":"Lichtenauer","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/scrt139","article-title":"The multi-differentiation potential of peripheral blood mononuclear cells","volume":"3","author":"Zhang","year":"2012","journal-title":"Stem Cell Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/bmb\/ldr012","article-title":"Stem cells in regenerative medicine: Introduction","volume":"98","author":"Ilic","year":"2011","journal-title":"Br. Med. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1634\/stemcells.18-6-390","article-title":"Immunologic profiles of effector cells and peripheral blood stem cells mobilized with different hematopoietic growth factors","volume":"18","author":"Gazitt","year":"2000","journal-title":"Stem Cells"},{"key":"ref_19","first-page":"1","article-title":"Endothelial progenitor cell therapy for chronic wound tissue regeneration","volume":"10","author":"Kaushik","year":"2019","journal-title":"Cytotherapy"},{"key":"ref_20","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":"ref_21","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jacc.2004.11.067","article-title":"Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 Diabetes Mellitus","volume":"45","author":"Fadini","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1177\/0271678X15610340","article-title":"What is a pericyte?","volume":"36","author":"Attwell","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_23","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. Cariovasc. Interv."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1161\/01.ATV.0000203513.29227.6f","article-title":"Differential Healing Activities of CD34+ and CD14+ Endothelial Cell Progenitors","volume":"26","author":"Awad","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.jcyt.2015.04.006","article-title":"Characterization of the Pall Celeris system as a point-of-care device for therapeutic angiogenesis","volume":"17","author":"Spaltro","year":"2015","journal-title":"Cytotherapy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1089\/ten.tec.2014.0245","article-title":"Limb Rescue: A New Autologous-Peripheral Blood Mononuclear Cells Technology in Critical Limb Ischemia and Chronic Ulcers","volume":"21","author":"Gentile","year":"2015","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_27","unstructured":"Di Pardo, A. (2017, January 4). Infusion of autologous-peripheral blood mononuclear cells: A new approach for limb salvage in patients with diabetes. Proceedings of the 7th International Diabetic Foot Congress Abu Dhabi, Abu Dhabi, United Arab Emirates."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nature07039","article-title":"Wound repair and regeneration","volume":"453","author":"Gurtner","year":"2008","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/ni.1937","article-title":"Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm","volume":"11","author":"Biswas","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nri2448","article-title":"Exploring the full spectrum of macrophage activation","volume":"8","author":"Mosser","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.12703\/P6-13","article-title":"The M1 and M2 paradigm of macrophage activation: Time for reassessment","volume":"6","author":"Martinez","year":"2014","journal-title":"F1000 Prime Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"150","DOI":"10.4103\/2231-0746.92782","article-title":"Role of macrophages in malignancy","volume":"1","author":"Dandekar","year":"2011","journal-title":"Annu. Maxillofac. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1089\/wound.2012.0407","article-title":"Disclosure of the Culprits: Macrophages-Versatile Regulators of Wound Healing","volume":"2","author":"Sindrilaru","year":"2013","journal-title":"Adv. Wound Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"Gordon","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3389\/fimmu.2019.01084","article-title":"Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages","volume":"10","author":"Orecchioni","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1126\/science.1117729","article-title":"A clonogenic bone marrow progenitor specific for macrophages and dendritic cells","volume":"311","author":"Fogg","year":"2006","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1146\/annurev.immunol.021908.132532","article-title":"Alternative activation of macrophages: An immunologic functional perspective","volume":"27","author":"Martinez","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"341308","DOI":"10.1155\/2015\/341308","article-title":"Current Concept and Update of the Macrophage Plasticity Concept: Intracellular Mechanisms of Reprogramming and M3 Macrophage \u201cSwitch\u201d Phenotype","volume":"2015","author":"Malyshev","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1189\/jlb.71.4.597","article-title":"Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages","volume":"71","author":"Raes","year":"2002","journal-title":"J. Leukoc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/ni.1671","article-title":"Toll-like receptor-induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens","volume":"9","author":"Qualls","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.immuni.2014.01.006","article-title":"Transcriptome-based network analysis reveals a spectrum model of human macrophage activation","volume":"40","author":"Xue","year":"2014","journal-title":"Immunity"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.4049\/jimmunol.181.6.3733","article-title":"Macrophage polarization in bacterial infections","volume":"181","author":"Benoit","year":"2008","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"834","DOI":"10.4049\/jimmunol.174.2.834","article-title":"Transcriptional profiling reveals complex regulation of the monocyte IL-1 beta system by IL-13","volume":"174","author":"Scotton","year":"2005","journal-title":"J. Immunol"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14978","DOI":"10.1073\/pnas.0809784106","article-title":"Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB","volume":"106","author":"Porta","year":"2009","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jablonski, K.A., Amici, S.A., Webb, L.M., De Dios Ruiz-Rosado, J., Popovich, P.G., Partida-Sanchez, S., and Guerau-de-Arellano, M. (2015). Novel Markers to Delineate Murine M1 and M2 Macrophages. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145342"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-380995-7.00001-X","article-title":"Macrophage proinflammatory activation and deactivation: A question of balance","volume":"108","author":"Valledor","year":"2010","journal-title":"Adv. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/path.4133","article-title":"Macrophage plasticity and polarization in tissue repair and remodelling","volume":"229","author":"Mantovani","year":"2013","journal-title":"J. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7303","DOI":"10.4049\/jimmunol.177.10.7303","article-title":"Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: New molecules and patterns of gene expression","volume":"177","author":"Martinez","year":"2006","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.cjtee.2017.06.001","article-title":"The molecular biology in wound healing and non-healing wound","volume":"20","author":"Qing","year":"2017","journal-title":"Chin. J. Traumatol."},{"key":"ref_52","first-page":"99","article-title":"Macrophage functions in wound healing","volume":"13","author":"Kloc","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3389\/fphys.2018.00419","article-title":"The role of macrophages in acute and chronic wound healing and interventions to promote pro-wound healing phenotypes","volume":"9","author":"Krzyszczyk","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e000743","DOI":"10.1161\/JAHA.113.000743","article-title":"Vasculogenic conditioning of peripheral blood mononuclear cells promotes endothelial progenitor cell expansion and phenotype transition of anti-inflammatory macrophage and T lymphocyte to cells with regenerative potential","volume":"3","author":"Masuda","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1007\/s10495-016-1292-8","article-title":"Peripheral blood mononuclear cell secretome for tissue repair","volume":"21","author":"Beer","year":"2016","journal-title":"Apoptosis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s00395-012-0292-2","article-title":"Secretome of apoptotic peripheral blood cells (APOSEC) attenuates microvascular obstruction in a porcine closed chest reperfused acute myocardial infarction model: Role of platelet aggregation and vasodilation","volume":"107","author":"Hoetzenecker","year":"2012","journal-title":"Basic Res. Cardiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1161\/01.CIR.0000058702.69484.A0","article-title":"Peripheral blood \u201cendothelial progenitor cells\u201d are derived from monocyte\/macrophages and secrete angiogenic growth factors","volume":"107","author":"Rehman","year":"2003","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1182\/blood-2012-06-436212","article-title":"Genetic programs expressed in resting and IL-4 alternatively activated mouse and human macrophages: Similarities and differences","volume":"121","author":"Martinez","year":"2013","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Mildner, C.S., Copic, D., Zimmermann, M., Lichtenauer, M., Direder, M., and Klas, K. (2022). Secretome of Stressed Peripheral Blood Mononuclear Cells Alters Transcriptome Signature in Heart, Liver, and Spleen after an Experimental Acute Myocardial Infarction: An in Silico Analysis. Biology, 11.","DOI":"10.3390\/biology11010116"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18016","DOI":"10.1038\/s41598-018-36928-6","article-title":"Different pro-angiogenic potential of \u03b3-irradiated PBMC-derived secretome and its subfractions","volume":"8","author":"Wagner","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1177\/0003319715595172","article-title":"Cell Therapy for Critical Limb Ischemia: A Meta-Analysis of Randomized Controlled Trials","volume":"67","author":"Liew","year":"2016","journal-title":"Angiology"},{"key":"ref_62","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":"ref_63","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1161\/CIRCINTERVENTIONS.112.968321","article-title":"Autologous CD34+ Cell Therapy for Critical Limb Ischemia Investigators. 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":"ref_64","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jdiacomp.2011.11.007","article-title":"Therapeutical potential of autologous peripheral blood mononuclear cell transplantation in patients with type 2 diabetic critical limb ischemia","volume":"26","author":"Ozturk","year":"2012","journal-title":"J. Diabetes Complicat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1055\/s-0032-1311646","article-title":"Therapeutic outcomes of transplanting autologous granulocyte colony-stimulating factor-mobilised peripheral mononuclear cells in diabetic patients with critical limb ischaemia","volume":"121","author":"Mohammadzadeh","year":"2013","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.jcyt.2013.05.017","article-title":"Peripheral blood-derived autologous stem cell therapy for the treatment of patients with late-stage peripheral artery disease-results of the short- and long-term follow-up","volume":"15","author":"Cserepes","year":"2013","journal-title":"Cytotherapy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1016\/j.jcyt.2014.07.011","article-title":"Bilateral administration of autologous CD133+ cells in ambulatory patients with refractory critical limb ischemia: Lessons learned froma a pilot, randomized, double-blind, placebo-controlled trial","volume":"16","author":"Raval","year":"2014","journal-title":"Cytotherapy"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ebiom.2018.08.038","article-title":"Purified CD34 + cells versus peripheral blood mononuclear cells in the treatment of angiitis-induced no-option critical limb ischaemia: 12-Month results of a prospective randomised singleblinded non-inferiority trial","volume":"35","author":"Dong","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0140-6736(02)09670-8","article-title":"Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: A pilot study and a randomised controlled trial","volume":"360","author":"Matsubara","year":"2002","journal-title":"Lancet"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1007\/s10047-006-0351-2","article-title":"Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs","volume":"9","author":"Kawamura","year":"2006","journal-title":"J. Artif. Organs"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1161\/01.RES.0000219901.13974.15","article-title":"Critical roles of muscle-secreted angiogenic factors in therapeutic neovascularization","volume":"98","author":"Tateno","year":"2006","journal-title":"Circ. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1253\/circj.71.1193","article-title":"Quality of Life Improvement and Long-Term Effects of Peripheral Blood Mononuclear Cell Transplantation for Severe Arteriosclerosis Obliterans in Diabetic Patients on Dialysis","volume":"71","author":"Hoshino","year":"2007","journal-title":"Circ. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/1358863X17752556","article-title":"Therapeutic efficacy of CD34+ cell-involved mononuclear cell therapy for no-option critical limb ischemia: A meta-analysis of randomized controlled clinical trials","volume":"23","author":"Pan","year":"2018","journal-title":"Vasc. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1161\/CIRCRESAHA.116.309045","article-title":"Autologous Cell Therapy for Peripheral Arterial Disease: Systematic Review and Meta-Analysis of Randomized, Nonrandomized, and Noncontrolled Studies","volume":"120","author":"Rigato","year":"2017","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jvs.2017.03.245","article-title":"Analysis of wound healing time and wound-free period as outcomes after surgical and endovascular revascularization for critical lower-limb ischemia","volume":"65","author":"Okazaki","year":"2017","journal-title":"J. Vasc. Surg."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Calabrese, V., Scuto, M., Trovato Salinaro, A., Dionisio, G., Modafferi, S., Ontario, M.L., Greco, V., Sciuto, S., Schmitt, C.P., and Calabrese, E.J. (2020). Hydrogen Sulfide and Carnosine: Modulation of Oxidative Stress and Inflammation in Kidney and Brain Axis. Antioxidants, 18.","DOI":"10.3390\/antiox9121303"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/1479-5876-11-281","article-title":"Wound outcome in combat injuries is associated with a unique set of protein biomarkers","volume":"11","author":"Chromy","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"a014217","DOI":"10.1101\/cshperspect.a014217","article-title":"MYC, metabolism, cell growth, and tumorigenesis","volume":"3","author":"Dang","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature13518","article-title":"Gene regulation: Fine-tuned amplification in cells","volume":"511","author":"Dang","year":"2014","journal-title":"Nature"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1182\/blood-2011-02-339911","article-title":"Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology","volume":"119","author":"Pello","year":"2012","journal-title":"Blood"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1137\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:00Z","timestamp":1760137560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,4]]},"references-count":80,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["diagnostics12051137"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12051137","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,4]]}}}