Autologous bone marrow mononuclear cell therapy is safe and promotes amputation- free survival in patients with critical limb ischemia Michael P. Murphy,

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Presentation transcript:

Autologous bone marrow mononuclear cell therapy is safe and promotes amputation- free survival in patients with critical limb ischemia Michael P. Murphy, MD, Jeffrey H. Lawson, MD, PhD, Brian M. Rapp, MD, Michael C. Dalsing, MD, Janet Klein, RN, Michael G. Wilson, PhD, Gary D. Hutchins, PhD, Keith L. March, MD, PhD Journal of Vascular Surgery Volume 53, Issue 6, Pages 1565-1574.e1 (June 2011) DOI: 10.1016/j.jvs.2011.01.074 Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 1 Bone marrow aspirate is loaded into a closed sterile 60-mL MarrowStim centrifugation tube in the operating room (A) and placed into the centrifuge device where the buffy coat is separated at 1500 rpm for 15 minutes (B). The autologous bone marrow mononuclear cell (ABMNC) rich buffy coat is aspirated from the tube (C), and 0.75 mL aliquots are delivered via intramuscular (IM) injections at 2-cm intervals, 1.5-cm deep into the gastrocnemius muscle, along the medial and lateral aspect of the index limb (D). Journal of Vascular Surgery 2011 53, 1565-1574.e1DOI: (10.1016/j.jvs.2011.01.074) Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 2 Change in first toe pressure (FTP), toe-brachial index (TBI), and ankle-brachial index (ABI) from baseline (mean ± SE). FTP increased by 10.2 ± 6.2 mm Hg (P = .02; A) and TBI increased by 0.10 ± 0.05 (P = .02; B) at week 12 from baseline. The ABI increased by 0.08 ± 0.04 at week 12 but was not significant (P = .73; C). ABMNC, Autologous bone marrow mononuclear cell. Journal of Vascular Surgery 2011 53, 1565-1574.e1DOI: (10.1016/j.jvs.2011.01.074) Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 3 Radiolabeled H2O15 positron emission tomography-computed tomography scan. A representative image of blood perfusion quantified with intra-arterial injection of H2O15 before autologous bone marrow mononuclear cell (ABMNC) treatment (A) in the left leg and after (B). A Blood Perfusion Index (BPI) was calculated by comparing the ratio of H2O15 peak tracer uptake level of the untreated: treated in the segment of the leg denoted by the dashed line. In this patient, the BPI increased from 0.38 at baseline to 0.54 (42%) at 12 weeks, concurrent with an increase in the ankle-brachial index (ABI) from 0 to 0.32 in the same period. Journal of Vascular Surgery 2011 53, 1565-1574.e1DOI: (10.1016/j.jvs.2011.01.074) Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 4 Correlation of bone marrow subpopulations and changes in perfusion. There was no correlation between total mononuclear cell (MNC) count and changes in ankle-brachial index (ABI) (R2 = 0.028; A). Using fluorescent activated cell sorting (FACS) analysis of endothelial progenitor cell (EPC) surface markers in ABMNCs we found a significant difference in KDR+ cells between responders to treatment as compared to non-responders (1.02 ± 0.39% vs 0.36 ± 0.12%; P = .008), respectively. There were no differences in CD34+ (4.21 ± 0.80% vs 3.97 ± 0.40%; P = .14) or CD133+ (0.59 ± 0.12% vs 0.68 ± 0.17%; P = .9) subpopulations between responders and nonresponders, respectively (B). Journal of Vascular Surgery 2011 53, 1565-1574.e1DOI: (10.1016/j.jvs.2011.01.074) Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 5 Changes in rest pain and quality of life. Using a 10-cm visual analogue scale, rest pain (RP) significantly decreased at 12 weeks by 2.2 ± 0.6 cm (P = .02; A). The VascuQol total score increased from 2.62 to 4.07 at 12 weeks (P = .008) (B). ABMNC, Autologous bone marrow mononuclear cell. Journal of Vascular Surgery 2011 53, 1565-1574.e1DOI: (10.1016/j.jvs.2011.01.074) Copyright © 2011 Society for Vascular Surgery Terms and Conditions

Fig 6 Ulcer healing. Nine patients with ulceration of the index limb were enrolled. Complete healing of the ulcer with re-epithelialization was achieved in three patients (33%) at 12 weeks. Representative photographs are shown of a 46-year-old woman with Buerger's disease and an ulcer on the right first toe at baseline (A1) and at 12 weeks (A2). FTP concurrently increased from 2 to 25 mm Hg in this period. A 73-year-old male with ulceration of the right heel with exposed calcaneus bone at baseline (B1) and at 12 weeks (B2). There was sufficient growth of granulation tissue to cover the calcaneus and support a split thickness skin graft (STSG). Although not considered a success of trial therapy alone, this case is presented to illustrate the potential of autologous bone marrow mononuclear cells (ABMNCs) in promoting wound healing via enablement of other procedures such as STSG. Journal of Vascular Surgery 2011 53, 1565-1574.e1DOI: (10.1016/j.jvs.2011.01.074) Copyright © 2011 Society for Vascular Surgery Terms and Conditions