Abstract
The therapeutic potential of mesenchymal stem cell (MSC) transplantation for the treatment of ischemic conditions such as coronary artery disease, peripheral arterial disease, and stroke has been explored in animal models and early-phase clinical trials. A substantial database documents the safety profile of MSC administration to humans in a large number of disease states. The mechanism of the therapeutic effect of MSC transplantation in ischemic disease has been postulated to be due to paracrine, immunomodulatory, and differentiation effects. This review provides an overview of the potential role of MSC-based therapy for critical limb ischemia (CLI), the comparison of MSC cellular therapy with angiogenesis gene therapy in CLI, and the proposed mechanism of action of MSC therapy. Preclinical efficacy data in animal models of hindlimb ischemia, current early-phase human trial data, and considerations for future MSC-based therapy in CLI will also be discussed.
Highlights
Mesenchymal stem cell (MSC) transplantation has been proposed as a novel treatment approach for tissue engineering and regenerative medicine for various disease states
Peripheral arterial disease: unmet clinical need Up to 10% of the population in the Western world suffers from peripheral arterial disease (PAD) and this represents a major health problem [1]. e prevalence of PAD has increased exponentially due to the increase in the prevalence of diabetes mellitus (DM) and an aging population. e increasing prevalence of PAD has resulted in a substantial increase in the consumption of health-care costs [2]
These results suggested that small numbers of MSCs engraft in the ischemic site following intravenous administration, that the beneficial effect of allogeneic transplantation may be attenuated by graft rejection, and that local administration may be the optimal approach for MSC-based therapy for critical limb ischemia (CLI)
Summary
Mesenchymal stem cell (MSC) transplantation has been proposed as a novel treatment approach for tissue engineering and regenerative medicine for various disease states. Xeno geneic MSCs administered intramuscularly to nonischemic thigh muscle remain confined to the site of injection; the highest level was detected after one day, and cells were detectable for up to three weeks [29] These results suggested that small numbers of MSCs engraft in the ischemic site following intravenous administration, that the beneficial effect of allogeneic transplantation may be attenuated by graft rejection, and that local administration may be the optimal approach for MSC-based therapy for CLI. Preclinical data Autologous, allogeneic, and xenogeneic administration of MSCs derived from various sources such as bone marrow, umbilical cord blood, fetal membrane, and adipose tissue has demonstrated significant improvement in mouse/rat models of hind-limb ischemia (Table 2). Lee and colleagues [89] later demonstrated that autologous adipose tissue-derived MSC transplantation in patients with Buerger’s disease and diabetic foot (a total of 3 × 108 cells) was feasible and safe It improved claudication walking distance, collateral vessel formation, wound healing, and clinical symptoms, especially pain relief. These OPGs should be adopted in clinical trials involving patients with CLI to allow direct comparison among trials
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