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

Abstract

In this multicenter, randomized, double-blind, placebo-controlled trial of autologous bone marrow cell therapy for CLI, the therapy was well tolerated without significant adverse events. The BMAC group demonstrated trends toward improvement in amputation, pain, quality of life, Rutherford classification, and ABI when compared with controls. This pilot allowed us to identify several areas for improvement for future trials and CLI studies. These recommendations include elimination of treadmill testing, stratification by Rutherford class, and more liberal inclusion of patients with renal insufficiency. Our strongest recommendation is that CLI studies that include Rutherford 4 patients should incorporate a composite endpoint reflecting pain and quality of life.

Cell Therapy and Critical Limb Ischemia: Evidence and Window of Opportunity in Obesity

“…As reported in many studies, intramuscular administration of BM-MNCs in ischemic limb improved clinical outcomes including improved ankle brachial index, pain-free walking distance/time, wound healing and limb salvage [73][74][75][76]. In support, recent studies confirmed the clinical improvement in patients with severe limb ischemia following intramuscular administration of BM-MNCs in terms of lower amputation rates and improved ankle-brachial index [77][78][79]. In contrast, a small randomized trial reported non-significant trends toward improved ankle brachial index, and wound healing in patients treated with BM-MNC [80].…”

Avoidance of Lower-Limb Amputation by Surgical Implantation of Autologous Stem Cells

“…He was enrolled in a pilot trial using bone marrow-derived stem cells, which were collected, processed, and immediately returned to the patient in the same procedure (2,7). In this procedure, a nonspecifi c mononuclear cell mix was implanted with minimal time spent outside the patient's body.…”

“…When it was determined that the patient had no additional revascularization options for limb salvage, he was enrolled in Harvest Technologies' "Feasibility Study of the Safety and Activity of Autologous Bone Marrow Aspirate Concentration (BMAC) for the Treatment of Critical Limb Ischemia Due to Peripheral Arterial Occlusive Disease" (2). His right ankle brachial index at the time of referral was 0.1, with a toe brachial index of 0.…”

Clinical Trials of Adult Stem Cell Therapy for Peripheral Artery Disease

“…since that time, numerous other studies have examined the efficacy and safety of cell therapy for Pad, with varying results (tables 1 and 2). [22][23][24][25][26][27][28][29][30][31][32][33] Most clinical trials of cell therapy for Pad have consisted of uncontrolled patient series, with few randomized, properly controlled studies. sample sizes have been relatively small, with most studies enrolling fewer than 50 patients.…”

“…[22][23][24][25][26][27][28][29][30][31][32][33] Procedures associated with cell therapy, such as bone marrow aspiration and injection, were generally well-tolerated by the patients, with few adverse events reported. hence, current data is promising, and safety concerns do not outweigh the promise of potential benefit, which must now be tested in definitive clinical trials.…”