Angiotensin-(1-7) stimulates hematopoietic progenitor cells in vitro and in vivo

Abstract

Effects of angiotensin (Ang)-(1-7), an AngII metabolite, on bone marrow-derived hematopoietic cells were studied. We identified Ang-(1-7) to stimulate proliferation of human CD34(+) and mononuclear cells in vitro. Under in vivo conditions, we monitored proliferation and differentiation of human cord blood mononuclear cells in NOD/SCID mice. Ang-(1-7) stimulated differentially human cells in bone marrow and accumulated them in the spleen. The number of HLA-I(+) and CD34(+) cells in the bone marrow was increased 42-fold and 600-fold, respectively. These results indicate a decisive impact of Ang-(1-7) on hematopoiesis and its promising therapeutic potential in diseases requiring progenitor stimulation.

Figures

Figure 1.

In vitro effect of Ang-(1–7) on cultured human cord blood derived CD34+ cells. The CD34+ cells were exposed to different concentrations of Ang-(1–7) in suspension culture, and then 5×104 cells/well were transferred to semi-solid medium. The number of large colonies without evidence of erythroid differentiation (A) and BFU-E formed (B) where assessed at various times after initiation of culture in semi-solid medium. *p<0.05 vs. control [0 mg/mL Ang-(1–7)]. In vivo effect of Ang-(1–7) on bone marrow and spleen cells in NOD/SCID mice. Representative flow cytometry density plots showing the effect of PBS and 10.8 μg Ang-(1–7)/mouse on isolated bone marrow cells (C) and spleen cells (D). The percentage of cells positive for human HLA-I and CD19 is indicated in the top right corner of each diagram.