Transforming growth factor-β boosts the functionality of human bone marrow-derived mesenchymal stromal cells

Transforming growth factor beta 1 (TGF beta 1) is a negative regulator of hematopoiesis, and yet, it is frequently found at the active sites of hematopoiesis. Here, we show for the first time that bone marrow-derived mononuclear cells (BM MNCs) secrete TGF beta 1 in response to erythropoietin (EPO). We further show that human bone marrow-derived mesenchymal stromal cells (BMSCs) briefly exposed to the conditioned medium of EPO-primed MNCs, or purified TGF beta 1, gain significantly increased hematopoiesis-supportive ability. Mechanistically, we show that this phenomenon involves TGF beta 1-mediated activation of nitric oxide (NO) signalling pathway in the BMSCs. The data suggest that EPO-MNC-TGF beta 1 could be one of the regulatory axes operative in the bone marrow microenvironment involved in maintaining the functionality of the resident BMSCs.