Long-term effects of repeated autologous transplantation of bone marrow cells in patients affected by peripheral arterial disease

Abstract

Long-term effects of autologous mononuclear bone marrow cell transplantation were studied in patients with severe peripheral arterial disease (PAD) and critical limb ischemia. Ten patients with end-stage disease were infused twice with autologous bone marrow cells and they completed the 12-month follow-up study. Substantial improvement of blood flow and increasing capillary densities were seen when compared with a concomitant control group comprising patients who did not enroll in the study. The ankle-brachial index (ABI) and pain-free walking distance improved significantly in treated patients. The improvement was sustained 12 months after treatment. These results confirm that the autologous bone marrow transplantation is an effective therapeutic strategy in critical limb ischemia.

Small Molecule Derived From Carboxyethylpyrrole Protein Adducts Promotes Angiogenesis in a Mouse Model of Peripheral Arterial Disease

“…Biological approaches using angiogenic proteins, such as VEGFA (vascular endothelial growth factor A), bFGF (basic fibroblastic growth factor), and SDF‐1α (stromal cell–derived factor 1α), have shown promising outcome in preclinical models but resulted in limited benefits in some clinical trials 2, 3, 4. Cell‐based approaches using bone marrow mononuclear cells have been tested in a number of small randomized clinical trials, but the results are controversial because the improvement in ankle‐branchial index was not consistent in some of the studies 5, 6, 7. Consequently, there is an increasing need for new angiogenic therapies.…”

Stem Cell Transplantation for the Treatment of Peripheral Arterial Disease

“…Ten patients with end-stage PAD underwent 2 BMMNC transplantations, while 10 matched patients served as controls [70]. In the treatment arm, there was a significant (p<0.05) improvement in ABI, claudication-free walking distance and capillary density, which were maintained at 12 months [70]. Eight patients with critical limb ischaemia (CLI) and no alternative treatment option received BMMNC transplantation into the gastrocnemius muscle [71].…”

“…At 2 years, ABI and TcPO 2 had not changed significantly, but there was a sustainable significant improvement in pain scale, ulcer size and pain-free walking distance [69]. Ten patients with end-stage PAD underwent 2 BMMNC transplantations, while 10 matched patients served as controls [70]. In the treatment arm, there was a significant (p<0.05) improvement in ABI, claudication-free walking distance and capillary density, which were maintained at 12 months [70].…”

Clinical Trials of Adult Stem Cell Therapy for Peripheral Artery Disease

“…[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.…”

“…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.…”