Emerging hurdles in stem cell therapy for peripheral vascular disease

Abstract

Indeed, while questions about safety, dose and administration route/timing/frequency are the first ones to be addressed when designing a stem-cell based clinical approach, there is accumulating evidence from recent (pre-)clinical studies that other issues may also be at stake. For instance, the choice of stem cells to be used and its precise mechanism of action, the need/possibility for concurrent tissue regeneration in case of irreversible tissue loss, the differentiation degree and specific vascular identity of the transplanted cells and the long-term survival of engrafted cells in the absence of a normal supportive tissue environment, should be well considered. Here, rather than presenting a comprehensive and extensive overview on the current literature on stem/progenitor cells and revascularization, we highlight some of the outstanding issues emerging from the recent (pre-)clinical literature that may co-determine the successful application of stem cells in a wide range of PVD patients in the future.

MAPC Transplantation Confers a more Durable Benefit than AC133+Cell Transplantation in Severe Hind Limb Ischemia

“…Unfortunately, clinical trials based on growth factor delivery have not yielded the expected results, thereby exposing the need for alternatives (5,13). Peripheral vascular disease (PVD) caused by inadequate blood supply to the limbs is a severe health Evidence indicating that adult vasculogenesis-vessel formation from endothelial progenitor cells (EPC)-is a problem in the Western world, affecting 3-10% of the population above the age of 60 (5).…”

“…Unfortunately, clinical trials based on growth factor delivery have not yielded the expected results, thereby exposing the need for alternatives (5,13). Peripheral vascular disease (PVD) caused by inadequate blood supply to the limbs is a severe health Evidence indicating that adult vasculogenesis-vessel formation from endothelial progenitor cells (EPC)-is a problem in the Western world, affecting 3-10% of the population above the age of 60 (5). Therapeutic revascuprocess that contributes to therapeutic neovascularization (6) has fueled the interest in the use of this alternalarization techniques, like laser revascularization, endovascular treatment, or bypass surgery, can in some cases tive paradigm for therapeutic revascularization.…”

“…HUVEC cells were grown (19). Nevertheless, as a result of the promising preclinical results, at least 40 clinical trials with (stem) cells in F12K medium (ATCC) supplemented with serum (10%), heparin (0.1 mg/ml), and ECGS (0.03 mg/ml) have already been started in PVD patients (5). Most of them have evaluated the potential of cord blood cells, and SMC were grown in DMEM high glucose (GIBCO-BRL) supplemented with 10% serum.…”

Endothelial Nitric Oxide Synthase Overexpression Restores the Efficiency of Bone Marrow Mononuclear Cell-Based Therapy

“…Clinical studies have demonstrated the safety, feasibility, and efficacy of intracoronary and intramuscular infusion of adult BMMNCs in patients with peripheral arterial disease, acute myocardial infarction, and ischemic cardiomyopathy. 1,2 However, despite the excitement surrounding the possible clinical use of BMMNCs, in atherosclerosis, diabetes mellitus, and other risk factors for cardiovascular diseases the availability of bone marrow and progenitor cells is reduced and their function impaired to varying degrees. 1,2 Moreover, the safety of BMMNCs treatment has been questioned by studies that found an increase in atherosclerotic plaque size after BMMNCs treatment.…”

“…1,2 However, despite the excitement surrounding the possible clinical use of BMMNCs, in atherosclerosis, diabetes mellitus, and other risk factors for cardiovascular diseases the availability of bone marrow and progenitor cells is reduced and their function impaired to varying degrees. 1,2 Moreover, the safety of BMMNCs treatment has been questioned by studies that found an increase in atherosclerotic plaque size after BMMNCs treatment. 3 This potentially hazardous dual effect of therapeutic neovascularization on atherogenesis is explained by the many common pathways of both mechanisms and has been named the Janus phenomenon.…”