Autologous bone marrow mononuclear cell therapy improves symptoms in patients with end-stage peripheral arterial disease and reduces inflammation-associated parameters |
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Affiliation: | 1. Department of Cardiology, Boston Children''s Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, United States;2. Department of Pediatrics, Wayne State University School of Medicine, Children''s Hospital of Michigan, Detroit, MI, United States;3. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children''s Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA, United States;1. Department of Obstetrics and Gynecology, Program in Women''s Oncology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, 101 Dudley Street, Providence, RI, USA;2. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The University of North Carolina at Chapel Hill, Campus Box 7572, Chapel Hill, NC 27599-7572, USA;3. Department of Pathology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, 101 Dudley Street, Providence, RI, USA |
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Abstract: | Background aimsThe purpose of this study was to evaluate the effect of autologous bone marrow mononuclear cells (BM-MNCs) on symptoms and perfusion indices in severely symptomatic patients with peripheral arterial disease (PAD) without further option for endovascular or surgical revascularization.MethodsOnly patients with severe symptomatic PAD (Fontaine class IIb-IV, Rutherford category 3–6) not amenable for revascularization were treated. Bone marrow from both cristae iliacae was harvested; MNCs were isolated by the Ficoll density-gradient method and transplanted by means of intra-arterial and intramuscular injection in the index limb. Functional (pain score, ulcer healing, maximum walking distance) and perfusion indices such as ankle-brachial-index and transcutaneous oxygen pressure were documented before and after BM-MNC therapy. Additionally, serum concentration of C-reactive protein and interleukin-6 were measured as markers of inflammation before and after BM-MNC treatment.ResultsSixteen consecutive patients (four women; mean age, 63.0 ± 13 years) were treated with a mean dose of 4.2 ± 2.2 × 108 BM-MNCs. At 6 months' follow-up, ankle-brachial-index, transcutaneous oxygen pressure and maximum walking distance significantly increased, whereas C-reactive protein and interleukin-6 conversely decreased (P < 0.01 versus baseline values), resulting in 88% limb salvage, 75% pain reduction and 71% complete wound healing and/or reduction of ulcer size. One major and one minor amputation were performed, both in patients with Rutherford category 6.ConclusionsAutologous BM-MNC therapy in patients with end-stage PAD improves tissue perfusion indices and decreases markers of inflammation. If our observations could be confirmed by large-scale, randomized controlled trials, BM-MNC transplantation could become an alternative therapeutic option for patients with end-stage PAD. |
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Keywords: | autologous mononuclear cells cell-based therapy critical limb ischemia end-stage peripheral arterial disease inflammation |
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