{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:43:41Z","timestamp":1790066621531,"version":"4.0.1"},"reference-count":116,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["GIA-13-01612"],"award-info":[{"award-number":["GIA-13-01612"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Critical limb ischemia (CLI), the most severe form of peripheral artery disease, is characterized by pain at rest and non-healing ulcers in the lower extremities. For patients with CLI, where the extent of atherosclerotic artery occlusion is too severe for surgical bypass or percutaneous interventions, limb amputation remains the only treatment option. Thus, cell-based therapy to restore perfusion and promote wound healing in patients with CLI is under intense investigation. Despite promising preclinical studies in animal models, transplantation of bone marrow (BM)-derived cell populations in patients with CLI has shown limited benefit preventing limb amputation. Early trials injected heterogenous mononuclear cells containing a low frequency of cells with pro-vascular regenerative functions. Most trials transferred autologous cells damaged by chronic disease that demonstrated poor survival in the ischemic environment and impaired function conferred by atherosclerotic or diabetic co-morbidities. Finally, recent preclinical studies suggest optimized blood vessel formation may require paracrine and\/or structural contributions from multiple progenitor cell lineages, angiocrine-secretory myeloid cells derived from hematopoietic progenitor cells, tubule-forming endothelial cells generated by circulating or vessel-resident endothelial precursors, and vessel-stabilizing perivascular cells derived from mesenchymal stem cells. Understanding how stem cells co-ordinate the myriad of cells and signals required for stable revascularization remains the key to translating the potential of stem cells into curative therapies for CLI. Thus, combination delivery of multiple cell types within supportive bioengineered matricies may represent a new direction to improve cell therapy strategies for CLI.<\/jats:p>","DOI":"10.1002\/stem.2751","type":"journal-article","created":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T08:09:12Z","timestamp":1512979752000},"page":"161-171","source":"Crossref","is-referenced-by-count":182,"title":["Concise Review: Cell Therapy for Critical Limb Ischemia: An Integrated Review of Preclinical and Clinical Studies"],"prefix":"10.1093","volume":"36","author":[{"given":"Mohammad","family":"Qadura","sequence":"first","affiliation":[{"name":"Division of Vascular Surgery, St. Michael's Hospital, Toronto, Ontario, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella C.","family":"Terenzi","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, St. Michael's Hospital, Toronto, Ontario, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subodh","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, Toronto, Ontario, Canada"},{"name":"Division of Cardiac Surgery, St. Michael's Hospital, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al-Omran","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, St. Michael's Hospital, Toronto, Ontario, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2186-3166","authenticated-orcid":false,"given":"David A.","family":"Hess","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, St. Michael's Hospital, Toronto, Ontario, Canada"},{"name":"Department of Surgery, University of Toronto, Toronto, Ontario, Canada"},{"name":"Molecular Medicine Research Laboratories, Krembil Centre for Stem Cell Biology, Robarts Research Institute, London, Ontario, Canada"},{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,1,3]]},"reference":[{"key":"2022022511594091800_stem2751-bib-0001","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":"2022022511594091800_stem2751-bib-0002","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1161\/CIRCRESAHA.116.303849","article-title":"Epidemiology of peripheral artery disease","volume":"116","author":"Criqui","year":"2015","journal-title":"Circ Res"},{"key":"2022022511594091800_stem2751-bib-0003","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1161\/CIRCRESAHA.115.303565","article-title":"Modulating the vascular response to limb ischemia: Angiogenic and cell therapies","volume":"116","author":"Cooke","year":"2015","journal-title":"Circ Res"},{"key":"2022022511594091800_stem2751-bib-0004","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jvs.2006.12.037","article-title":"Inter-society consensus for the management of peripheral arterial disease (TASC II)","volume":"45 Suppl S","author":"Norgren","year":"2007","journal-title":"J Vasc Surg"},{"key":"2022022511594091800_stem2751-bib-0005","doi-asserted-by":"crossref","first-page":"1S","DOI":"10.1016\/j.jvs.2014.12.006","article-title":"Society for vascular surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities management of asymptomatic disease and claudication. 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