Background: Recent studies have suggested that bone marrow stromal cells (BMSC) have the potential to differentiate into endothelial cells. However, the physiologic functions of the endothelial-like cells derived from BMSC have not been well studied.
Methods: Human BMSC were induced to differentiate into endothelial-like cells with a combination of cytokines. Morphologic, phenotypic, ultrastructural and functional characterizations of the endothelial-like cells were made.
Results: Human BMSC were successfully differentiated into cells with endothelial-like morphology and phenotype in vitro. These cells expressed various endothelial cell functions in vitro, such as release of von Willebrand factor (vWF) mediated by histamine, acetylated low-density lipoprotein (acLDL) uptake, binding of Ulex europaeus agglutinin-1 (UEA-1) and in vitro capillary formation. The cells also acquired important ultrastructural and physiologic properties of endothelial cells as they contained Weibel-Palade bodies, abundant mitochondria with a homogeneous mitochondrial matrix, diluted rough endoplasmic reticula, enlarged Golgi complexes, a regular arrangement of microfilaments and many surface cytoplasmic processes and plasmalemmal vesicles, as well as intercellular tight junctions and desmosome-like structures. Subcutaneous implantation of the endothelial-like cells in Matrigel plugs in immunodeficient mice resulted in the formation of functional blood vessels that contained erythrocytes. Moreover, these cells contributed to in vivo neovascularization during wound healing in rabbit ischemic hindlimb models.
Discussion: Physiologic features of the endothelial-like cells derived from BMSC suggest the potential use of these cells as a functional cell source for therapeutic applications.