{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:00:39Z","timestamp":1792706439169,"version":"4.5.0"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,4,14]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Critical limb ischemia is a life-threatening complication of peripheral arterial disease. In patients who are ineligible for revascularization procedures, there are few therapeutic alternatives, leading to amputations and death.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To provide a systematic review of the literature and a meta-analysis of studies evaluating safety and efficacy of autologous cell therapy for intractable peripheral arterial disease\/critical limb ischemia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We retrieved 19 randomized controlled trials (837 patients), 7 nonrandomized trials (338 patients), and 41 noncontrolled studies (1177 patients). The primary outcome was major amputation. Heterogeneity was high, and publication bias could not be excluded. Despite these limitations, the primary analysis (all randomized controlled trials) showed that cell therapy reduced the risk of amputation by 37%, improved amputation-free survival by 18%, and improved wound healing by 59%, without affecting mortality. Cell therapy significantly increased ankle brachial index, increased transcutaneous oxygen tension, and reduced rest pain. The secondary analysis (all controlled trials; n=1175 patients) shows that there may be potential to avoid \u22481 amputation\/year for every 2 patients successfully treated. The tertiary analysis (all studies; n=2332 patients) precisely estimated the changes in ankle brachial index, transcutaneous oxygen tension, rest pain, and walking capacity after cell therapy. Intramuscular implantation appeared more effective than intra-arterial infusion, and mobilized peripheral blood mononuclear cells may outperform bone marrow\u2013mononuclear cells and mesenchymal stem cells. Amputation rate was improved more in trials wherein the prevalence of diabetes mellitus was high. Cell therapy was not associated with severe adverse events. Remarkably, efficacy of cell therapy on all end points was no longer significant in placebo-controlled randomized controlled trials and disappeared in randomized controlled trials with a low risk of bias.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Although this meta-analysis highlights the need for more high-quality placebo-controlled trials, equipoise may no longer be guaranteed because autologous cell therapy has the potential to modify the natural history of intractable critical limb ischemia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.309045","type":"journal-article","created":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T03:03:34Z","timestamp":1484708614000},"page":"1326-1340","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":210,"title":["Autologous Cell Therapy for Peripheral Arterial Disease"],"prefix":"10.1161","volume":"120","author":[{"given":"Mauro","family":"Rigato","sequence":"first","affiliation":[{"name":"From the Department of Medicine, University of Padova, Italy (M.R., G.P.F.); and Diabetology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy (M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Monami","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Padova, Italy (M.R., G.P.F.); and Diabetology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy (M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Paolo","family":"Fadini","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Padova, Italy (M.R., G.P.F.); and Diabetology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy (M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","article-title":"2016 aha\/acc guideline on the management of patients with lower extremity peripheral artery disease: A report of the american college of cardiology\/american heart association task force on clinical practice guidelines.","author":"Gerhard-Herman MD","year":"2016","unstructured":"Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME. 2016 aha\/acc guideline on the management of patients with lower extremity peripheral artery disease: A report of the american college of cardiology\/american heart association task force on clinical practice guidelines. 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