Basic Science for Clinicians Stem Cell Therapy for Vascular Regeneration Adult, Embryonic, and Induced Pluripotent Stem Cells

Broadly speaking, vascular regeneration includes the restoration of normal vascular function and structure, the reversal of vascular senescence, and the growth of new blood vessels. Therapeutic applications of vascular regeneration for coronary or peripheral arterial diseases are directed to relieving symptoms of ischemia; preventing target-organ damage due to hypoxia, reperfusion, or capillary leak; and avoiding cardiovascular catastrophes due to acute thrombosis, embolism, plaque rupture, or dissection. Clinicians have sought methods to harness the potential of therapeutic vascular regeneration, but studies focused on gene therapy or small molecular approaches have largely failed thus far. Recently, efforts have shifted to stem cell–based approaches given their theoretical capacity to replicate, differentiate, and form new blood vessels in a directed fashion. Initial preclinical studies evaluated the pluripotent embryonic stem cell (ESC) and the more lineage-committed “adult” stem cells, which include the endothelial progenitor cells (EPCs) found within the bone marrow. Early clinical trials indicate some benefit of EPC therapy in patients with ischemic or cardiomyopathic disease. In the meantime, scientific interest has shifted to a newly described class of stem cell, the induced pluripotent stem cell (iPSC). This fascinating cell is derived from terminally differentiated adult somatic cells that are “reprogrammed” to an embryonic-like state with transcription factors that govern cell differentiation. Interest in iPSCs is high because these cells are autologous (do not require immunosuppression when delivered), have pluripotential (can differentiate into tissue from each of the 3 germline lineages), are noncontroversial (are derived from adult tissue), and come from a plentiful source (are derived from any adult cell [eg, skin fibroblasts]). The focus of this review is on the use of stem cell therapies for the growth of new blood vessels (ie, angiogenesis, vasculogenesis, and arteriogenesis). In particular, we will focus on the promise of iPSCs for cell-based vascular regeneration compared with other stem cell approaches.