Cyclic GMP signalling in human ES and iPS-derived vascular cells

Background Previously we demonstrated the differentiation pathway of mouse, monkey and human ES cells to vascular cell components [1-3]. In addition, we showed the therapeutic potential of these ES-derived vascular cells. When transplanted in mouse hind-limb ischemia model, these cells were incorporated in host vessels in the ischemic lesion and contributed to host neovascular formations [4]. In these our studies, however, primary cultured human adult vascular endothelial cells were not incorporated in host vessels and did not have same therapeutic effect as ES-derived vascular endothelial cells (See Figure 1). In addition, ES-derived vascular endothelial cells had higher viability against oxidative stress and higher ability to re-endothelization in wound-healing model than adult vascular endothelial cells. We supposed that ES-derived young vascular endothelial cells have higher ability as the cell source for vascular regeneration than adult aged vascular endothelial cells. On the other hand, we previously reported significance and therapeutic potential of the natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration. Natriuretic peptides (NP) significantly stimulated capillary network formation of cultured endothelial cells by cGK stimulation and subsequent Erk12 activation [5]. Therefore, we are now investigating the difference of NO/cGMP and NP/ cGMP pathway between ES-derived vascular cells and adult vascular cells. In addition, human induced pluripotent stem (iPS) cells are a novel stem cell population derived from human adult somatic cells through reprogramming using a defined set of transcription factors [6]. Our aim was to determine the features of the directed differentiation of human iPS cells into vascular endothelial cells and mural cells, and to compare that process with human ES cells.