Cell Therapy for Chronic Limb-Threatening Ischemia: Current Evidence and Future Directions

Abstract

Cell-based therapies have gained interest as a potential treatment method in cardiovascular disease in the past two decades, peripheral artery disease amongst others. Initial pre-clinical and small pilot clinical studies showed promising effects of cell therapy in peripheral artery disease and chronic limb-threatening ischemia in particular. However, these promising results were not corroborated in larger high quality blinded randomized trials. This has led to a shift of the field towards more sophisticated cell products, especially mesenchymal stromal cells. Mesenchymal stromal cells have some important benefits, making these cells ideal for regenerative medicine, e.g., potential for allogeneic application, loss of disease-mediated cell dysfunction, reduced production costs, off-the-shelf availability. Future high quality and large clinical studies have to prove the efficacy of mesenchymal stromal cells in the treatment of peripheral artery disease. Stem Cells Translational Medicine 2018;7:842-846.

Figure 1

Different potential modes of action of cell therapy. (A): Direct angiogenesis through introduction of endothelial‐like cells that will form new capillaries through vasculogenesis and fill endothelial defects. (B): Indirect angiogenesis through introduction of monocyte‐like cells, that will remodel the extracellular matrix and will recruit and guide new endothelial sprouts. (C): Indirect angiogenesis through paracrine effects, including modulation of monocyte differentiation and recruitment of endothelial cells.