Invited commentary

Abstract

The multilevel disease seen in patients with critical limb ischemia (CLI) is difficult to address using endovascular therapy or open bypass because of anatomic constraints, lack of appropriate conduit, and significant comorbidities. Therapeutic arteriogenesis using cellular therapy has been the focus of research because single growth factor therapy has failed to improve outcomes in randomized controlled trials. Mesenchymal stromal cells (MSCs) are of particular interest because of their ability to secrete multiple angiogenic and arteriogenic factors and to stimulate both angiogenesis and arteriogenesis in vitro and in vivo in small animal models of hindlimb ischemia. However, there are two major limitations to using MSCs, harvest and generation of sufficient numbers of MSCs in a clinically relevant time frame and functional capacity of autogenous MSCs in unfavorable conditions common to patients with CLI, hypertension, hyperlipidemia, ischemia, and diabetes. The current article addresses these concerns by showing that use of pooled human platelet lysate as a human serum supplement rather than the more traditional fetal bovine serum significantly improved proliferation of MSCs harvested from the tibia of patients with CLI with or without concomitant diabetes undergoing amputation, although it was still worse than that seen in MSCs from healthy donors. The authors further demonstrate that the isolated CLI MSCs secrete similar levels of angiogenic and arteriogenic growth factors and stimulate angiogenesis in an in vitro coculture sprouting assay to MSCs from healthy donors. What remains lacking is the translational component back into humans, demonstrating that these isolated MSCs expanded using pooled human platelet lysate can stimulate therapeutic arteriogenesis in the unfavorable milieu of a CLI patient as opposed to a healthy animal subjected to experimental arterial ligation. However, this work is an important first step toward that translation and a tantalizing window into a true cell-based therapy for limb salvage. Expansion and angiogenic potential of mesenchymal stem cells from patients with critical limb ischemiaJournal of Vascular SurgeryVol. 65Issue 3PreviewCritical limb ischemia (CLI) is a life- and limb-threatening condition affecting 1% to 10% of the population with peripheral arterial disease. Traditional revascularization options are not possible for up to 50% of CLI patients, in which case, the use of cellular therapies, such as bone marrow-derived mesenchymal stem cells (MSCs), hold great promise as an alternative revascularization therapy. However, no randomized, controlled phase 3 trials to date have demonstrated an improvement in limb salvage with cellular therapies. Full-Text PDF Open Archive