Platelet-derived growth factor plays a critical role to convert bone marrow cells into glomerular mesangial-like cells

Background. Despite increasing interest in bone marrow-derived stem cells, little is known about critical factors that determine their fates both in vitro and in vivo. Recently, we have reported that bone marrow is a reservoir for glomerular mesangial cells in rats. To find a key factor responsible for the differentiation of bone marrow-derived cells into mesangial cells, we established a new culture system of rat bone marrow, which is based on serial replating and differential attachment to collagen types I and IV. Methods. Bone marrow cells that did not adhere to collagen type I within 24 hours were transferred to collagen type IV-coated dishes. Then, the cells attached to collagen type IV in the following 24 hours were maintained in the presence of 2% horse serum, 200 ng/mL of platelet-derived growth factor (PDGF) BB, and 1 mumol/L of all-trans retinoic acid. In vivo effect of PDGF-B was also examined by introducing human PDGF-B gene into glomeruli. Results. After cultivation under the above condition for 7 days, approximately 14% of cells expressed Thy-1 and desmin, both of which are markers for rat mesangial cells. Thy-1(++) /desmin(+) cells were stellate-shaped, and contracted in response to angiotensin II. When human PDGF-B gene was overexpressed in the glomeruli of chimeric rats whose bone marrow was transplanted from enhanced green florescent protein (EGFP) transgenic rats, the number of EGFP mesangial cells increased. This effect was canceled by prior introduction of a neutralizing molecule that is composed of PDGF receptor-beta ligand binding site and IgG-Fc. Conclusion. These results indicate that PDGF-B plays a critical role to direct bone marrow-derived cells toward mesangial-like cells both in vitro and in vivo.