{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:50:48Z","timestamp":1791154248143,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Interventions"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Forty patients with critical limb ischemia were included in a multicenter, phase II, double-blind, randomized-start trial to receive either intraarterial administration of BM-MNC or placebo followed by active treatment with BM-MNC (open label) after 3 months. Intraarterial administration of BM-MNC did not significantly increase ankle-brachial index and, thus, the trial missed its primary end point. However, cell therapy was associated with significantly improved ulcer healing (ulcer area, 3.2\u00b14.7 cm\n              <jats:sup>2<\/jats:sup>\n              to 1.89\u00b13.5 cm\n              <jats:sup>2<\/jats:sup>\n              [\n              <jats:italic>P<\/jats:italic>\n              =0.014] versus placebo, 2.92\u00b13.5 cm\n              <jats:sup>2<\/jats:sup>\n              to 2.89\u00b14.1 cm\n              <jats:sup>2<\/jats:sup>\n              [\n              <jats:italic>P<\/jats:italic>\n              =0.5]) and reduced rest pain (5.2\u00b11.8 to 2.2\u00b11.3 [\n              <jats:italic>P<\/jats:italic>\n              =0.009] versus placebo, 4.5\u00b12.4 to 3.9\u00b12.6 [\n              <jats:italic>P<\/jats:italic>\n              =0.3]) within 3 months. Limb salvage and amputation-free survival rates did not differ between the groups.\n            <\/jats:p>\n            <jats:p>\n              Repeated BM-MNC administration and higher BM-MNC numbers and functionality were the only independent predictors of improved ulcer healing. Ulcer healing induced by repeated BM-MNC administration significantly correlated with limb salvage (\n              <jats:italic>r<\/jats:italic>\n              =0.8;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Intraarterial administration of BM-MNC is safe and feasible and accelerates wound healing in patients without extensive gangrene and impending amputation. These exploratory findings of this pilot trial need to be confirmed in a larger randomized trial in patients with critical limb ischemia and stable ulcers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT00282646.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circinterventions.110.958348","type":"journal-article","created":{"date-parts":[[2011,1,5]],"date-time":"2011-01-05T01:54:35Z","timestamp":1294192475000},"page":"26-37","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":219,"title":["Intraarterial Administration of Bone Marrow Mononuclear Cells in Patients With Critical Limb Ischemia"],"prefix":"10.1161","volume":"4","author":[{"given":"Dirk H.","family":"Walter","sequence":"first","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Krankenberg","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn O.","family":"Balzer","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kalka","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Tonn","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Seeger","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Dimmeler","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edelgard","family":"Lindhoff-Last","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas M.","family":"Zeiher","sequence":"additional","affiliation":[{"name":"From the Division of Cardiology and Angiology (D.H.W., F.S., S.D., E.L.-L., A.M.Z.) and Department of Radiology (J.O.B.), University of Frankfurt, Frankfurt, Germany; Hamburg University Cardiovascular Center: Prof Mathey, Prof Schofer (D.H.W., H.K., M.S.), Hamburg, Germany; Vascular Medicine (C.K., I.B.), Inselspital Bern, Bern, Germany; and Institute for Transfusion Medicine and Immunohematology, Frankfurt Red Cross Blood Donor Service, Baden-Wuerttemberg-Hessen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the PROVASA Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.174526"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1078-5884(97)80067-6"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105243442108"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e318153fdcb"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09670-8"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.9.2155"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-02-0137"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2006.06.023"},{"key":"e_1_3_4_10_2","first-page":"51","article-title":"Intramuscular or combined intramuscular\/intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia","volume":"49","author":"Van Tongeren RB","year":"2008","unstructured":"Van Tongeren RB, Hamming JF, Fibbe WE, Van Weel V, Frerichs SJ, Stiggelbout AM, Van Bockel JH, Lindeman JH. 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