A Phase II Trial of Autologous Transplantation of Bone Marrow Stem Cells for Critical Limb Ischemia: Results of the Naples and Pietra Ligure Evaluation of Stem Cells Study

Abstract

Critical limb ischemia (CLI) is a vascular disease affecting lower limbs, which is going to become a demanding challenge because of the aging of the population. Despite advances in endovascular therapies, CLI is associated with high morbidity and mortality. Patients without direct revascularization options have the worst outcomes. To date, 25%–40% of CLI patients are not candidates for surgical or endovascular approaches, ultimately facing the possibility of a major amputation. This study aimed to assess the safety and efficacy of autologous bone marrow (BM) transplantation performed in “no‐option” patients, in terms of restoring blood perfusion by collateral flow and limb salvage. A multicenter, prospective, not‐controlled phase II study for no‐option CLI patients was performed. Patients were subjected to intra‐arterial infusion of autologous bone marrow and followed for 12 months after the treatment. Variation of blood perfusion parameters, evaluated by laser Doppler flowmetry or transcutaneous oximetry, was set as the primary endpoint at 12 months after treatment and amputation‐free survival as the secondary endpoint. Sixty patients were enrolled and treated with BM transplantation, showing improvement in objective and subjective measures of perfusion. Furthermore, survival analysis demonstrated improved amputation‐free survival rates (75.2%) at 12 months after the treatment. This study provides further evidence that autologous bone marrow transplantation is well tolerated by CLI patients without adverse effects, demonstrating trends toward improvement in perfusion and reduced amputation rate, confirming the feasibility and safety of the procedure.

<p>One-Year Outcomes of Peripheral Endovascular Device Intervention in Critical Limb Ischemia Patients: Sub-Analysis of the LIBERTY 360 Study</p>

“…Approximately 18 million Americans have peripheral artery disease (PAD) and 2 million of these patients suffer from critical limb ischemia (CLI), 1,2 the end stage of PAD. 3 CLI is highly prevalent in older patients with diabetes and/or end-stage renal disease 4 and is associated with high risk of amputation and mortality.…”

Intrastriatal Transplantation of Adult Human Neural Crest-Derived Stem Cells Improves Functional Outcome in Parkinsonian Rats

“…Although restricted in their differentiation potential, these stem cells possess the capability to self‐renew and give rise to multiple specialized cell types [20], thereby exhibiting remarkably low tumorigenicity [16, 18, 21, 22]. Another advantage of adult stem cells is that their application allows autologous cell transplantation, avoiding the need for long‐term immunosuppression in the patient [23–26]. With respect to PD treatment strategies, rat mesenchymal stem cells (MSCs) were recently reported to differentiate into tyrosine hydroxylase‐positive (TH + ) DA neurons in a 6‐hydroxydopamine (6‐OHDA) rat model, accompanied by slight improvement of motor deficits after 8 weeks [27].…”

SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs

“…Pilot human studies have shown that autologous transplantation of bone marrow cells induced therapeutic angiogenesis in patients with critical limb ischemia [3]. hMSCs are pluripotent progenitors that can differentiate into a variety of cell types and have been shown to promote angiogenesis both in vivo and in vitro.…”