scholarly journals Early results and lessons learned from a multicenter, randomized, double-blind trial of bone marrow aspirate concentrate in critical limb ischemia

2011 ◽  
Vol 54 (6) ◽  
pp. 1650-1658 ◽  
Author(s):  
Mark D. Iafrati ◽  
John W. Hallett ◽  
George Geils ◽  
Gregory Pearl ◽  
Alan Lumsden ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Critical Limb Ischemia ◽  
Bone Marrow Aspirate ◽  
Limb Ischemia ◽  
Lessons Learned ◽  
Double Blind Trial ◽  
Double Blind ◽  
Blind Trial ◽  
Bone Marrow Aspirate Concentrate ◽  
Early Results

scholarly journals Bone Marrow Aspirate Concentrate in Critical Limb Ischemia: Results of a Multicenter Randomized Double-Blind Trial

2010 ◽  
Vol 52 (4) ◽  
pp. 1123 ◽  
Author(s):  
Mark D. Iafrati ◽  
Dennis Bandyk ◽  
Eric Benoit ◽  
George Geils ◽  
John (Jeb) Hallett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Critical Limb Ischemia ◽  
Bone Marrow Aspirate ◽  
Limb Ischemia ◽  
Double Blind Trial ◽  
Double Blind ◽  
Blind Trial ◽  
Bone Marrow Aspirate Concentrate

Abstract 305: Cytokine Response to Concentrated Bone Marrow Aspirate Injections in Patients With Critical Limb Ischemia

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
S. Keisin Wang ◽  
Linden Green ◽  
Cliff Babbey ◽  
Raghu Motaganahalli ◽  
Praveen Kusumanchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Critical Limb Ischemia ◽  
Bone Marrow Aspirate ◽  
Limb Ischemia ◽  
Phase Iii ◽  
Response To Treatment ◽  
Surgical Revascularization ◽  
Double Blind ◽  
Tissue Ischemia ◽  
Concentrated Bone Marrow

Objective: No medical intervention is approved for patients who suffer from critical limb ischemia (CLI) without a surgical revascularization option. Concentrated bone marrow aspirate (cBMA) injections have demonstrated safety and efficacy in increasing 1-year amputation-free survival (AFS) in the phase III multicenter, double blind, randomized controlled MOBILE trial. The response to cBMA injection is described herein. Methods: A murine (IL-2Rγ -/- ) hind-limb ischemia model was employed to assay blood and tissue levels of angiogenic markers after MarrowStim TM derived cBMA injection. Responders to therapy were selected by cutaneous laser Doppler. Animals were sacrificed at various time points post-injection during which blood and distal limb tissue was harvested. 10 patients were enrolled into the MOBILE Continuing Access trial from May to December 2016 and received cBMA injections into the ischemic limb. Blood was collected at days 1, 3, 7, 14, 45, 60, and 90. Endothelial progenitor cells (EPCs) and protein markers of tissue ischemia were assayed by FACS and ELISA respectively. Results: In mice, cBMA produced a marked increase in gross tissue survival, capillary density, and perfusion compared to the control limb despite low engraftment of human cells. There was no inflammatory infiltration at any of the injection sites. Subanalysis of groups that had differing responses demonstrated crucial increases in FGF-2, VEGF, angiopoietin-2, IL-1β, and TNF-α. 7 subjects donated adequate of blood samples for FACS analysis; of this cohort, 5 patients had demonstrable increases in their EPC to non-EPC ratios immediately post-treatment. No statistically significant changes in FGF, VEGF, ANG1/2, PDGF, and GM-CSF was observed in the systemic circulation. Conclusions: cBMA has demonstrated efficacy in increasing 1-year AFS in CLI patients without surgical revascularization options. However, the response to treatment is variable and further studies are required to predict those who would benefit the most from cBMA.

scholarly journals Bone marrow aspirate injection for treatment of critical limb ischemia with comparison to patients undergoing high-risk bypass grafts

2015 ◽  
Vol 61 (1) ◽  
pp. 134-137 ◽  
Author(s):  
Kristina A. Giles ◽  
Eva M. Rzucidlo ◽  
Philip P. Goodney ◽  
Daniel B. Walsh ◽  
Richard J. Powell
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Critical Limb Ischemia ◽  
Bone Marrow Aspirate ◽  
Limb Ischemia ◽  
Bypass Grafts

Intraarterial Versus Intramuscular Delivery of Autologous Bone Marrow Blood to Patients with Critical Limb Ischemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2999-2999
Author(s):  
Martin Mistrik ◽  
Juraj Madaric ◽  
Andrej Klepanec ◽  
Ingrid Olejarova ◽  
Marcela Skrakova
Keyword(s):  
Bone Marrow ◽  
Limb Salvage ◽  
Critical Limb Ischemia ◽  
Bone Marrow Aspirate ◽  
Autologous Bone Marrow ◽  
Limb Ischemia ◽  
Pain Scale ◽  
Cd34 Cells ◽  
Autologous Bone ◽  
Bone Marrow Blood

Abstract Abstract 2999 Introduction: Autologous bone marrow cell application has been proposed as an alternative therapy in patients (pts) with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization, but the way of their administration is currently unresolved. The aim of our study is to compare intramuscular (i.m.) and intraarterial (i.a.) bone marrow blood (BMB) delivery. Methods: Fifty nine patients (median age 67 years, range 38 – 89; gender M :F = 50 :9) with advanced CLI (Rutherford category 5, 6) not eligible for revascularization underwent analgosedation with profolol and total of 240 ml of BMB from both posterior iliac crests were harvested and stabilized with heparin. Bone marrow aspirate was processed with SmartPreP2 Bone Marrow Aspirate Concentrate System (Harvest, Plymouth, MA) – gradient density centrifugation to provide 40 ml of BMB concentrate (BMBc) within 15–20 minutes. Patients were randomized to treatment with 40 ml of BMBc either using local i.m. or i.a. infusion. Primary end points were limb salvage and wound healing. Secondary end points included changes in transcutaneous oxygen pressure (tcpO2), quality of life questionnaire (EQ 5D), ankle-brachial index (ABI), and pain scale (0–10 scale). Patients with limb salvage and wound healing were considered as responders to BMBc therapy. Results: Fifty nine collected BMB contained median mononucleated cell number 35, 8 × 109/l (range 12, 5 – 79, 8) and CD34+ cells 237, 25 × 106/l (range 57, 2 – 694, 3). Processing of BMB reduced to volume from 240 ml to 40 ml (e.g. 6x) and increased concentration of mononucleated cells and CD34+ cells (2, 9x). According to the randomization BMBc was administered i.m. (24 patients) into the ischemic limb or by means of i.a. infusion (800ml/hour) through the catheter positioned into the popliteal artery (25 patients). Since procedure 41 patients could reach 180 days follow up, 4 patients died from unrelated reason to study and 37 patients were evaluable for response. Twenty seven of 37 had limb salvage (73%). There was significant improvement in tcpO2 (15±10 to 29±13mmHg, p<0.001), in pain scale (4.4±2.6 to 0.9±1.4, p<0.001) and EQ 5D (51±15 to 70±13, p<0.001), and significant decrease in Rutherford category of CLI (5.0±0.2 to 4.3±1.6, p<0.01). There were no differences among functional parameters in patients undergoing i.m. versus i.a. delivery. Responders (n=27) vs. nonresponders (n=10) received higher CD34+ cells amounts in the bone marrow concentrate (29±15×10^6 vs 17±12×10^6, p<0.05), but similar number of total nucleated cells (4.3±1.4×10^9 vs 4.1±1.2×10^9, p=0.66). Responders had significantly lower C-reactive protein level (CRP 18±28 vs 100±96 mg/l, p<0.05) and white blood cell counts (8.3±2.1×10^9/l vs 12.3×4.5×10^9/l, p<0.05) at the time of study procedure. Conclusions: Autologous bone marrow blood harvest and administration is safe. There is no difference in i.m. versus i.a. application, both methods of autologous BMB delivery are effective in pts with CLI. Higher CD34+ cell content in BMBc and lower degree of inflammation are associated with good response to BMB application. Funding of project “Transplantation of autologous bone-marrow stem cells in patients with critical limb ischemia” ITMS code 26240220023 is supported by Operational programme Research and Innovation from European Regional Development Fund. Disclosures: No relevant conflicts of interest to declare.

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