Concise review: therapeutic potential of adipose tissue-derived angiogenic cells

Abstract

Inadequate blood supply to tissues is a leading cause of morbidity and mortality today. Ischemic symptoms caused by obstruction of arterioles and capillaries are currently not treatable by vessel replacement or dilatation procedures. Therapeutic angiogenesis, the treatment of tissue ischemia by promoting the proliferation of new blood vessels, has recently emerged as one of the most promising therapies. Neovascularization is most often attempted by introduction of angiogenic cells from different sources. Emerging evidence suggests that adipose tissue (AT) is an excellent reservoir of autologous cells with angiogenic potential. AT yields two cell populations of importance for neovascularization: AT-derived mesenchymal stromal cells, which likely act predominantly as pericytes, and AT-derived endothelial cells (ECs). In this concise review we discuss different physiological aspects of neovascularization, briefly present cells isolated from the blood and bone marrow with EC properties, and then discuss isolation and cell culture strategies, phenotype, functional capabilities, and possible therapeutic applications of angiogenic cells obtained from AT.

Figure 1.

The processes of angiogenesis, vasculogenesis, and arteriogenesis. New microvessels are generated from pre-existing vasculature by the proliferation and migration of mature ECs in the classic process of new vessel growth, angiogenesis. Vasculogenesis involves participation of undifferentiated EPCs, which circulate to sites of new vessel growth, where they differentiate into mature ECs. Arteriogenesis involves the expansive growth of collateral arteries by sprouting of pre-existing vessels to form collateral bridges between arterial networks via the migration and proliferation of ECs and SMCs. Growth factors and cytokines released endogenously in response to tissue ischemia act to promote neovascularization. Abbreviations: Ang 1, angiopoietin-1; EC, endothelial cell; EPC, endothelial progenitor cell; FGF, fibroblast growth factor; HIF, hypoxia-inducible factor; SMC, smooth muscle cell; VEGF, vascular endothelial growth factor.