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  • Title: Platelet-derived growth factor plays a critical role to convert bone marrow cells into glomerular mesangial-like cells.
    Author: Suzuki A, Iwatani H, Ito T, Imai E, Okabe M, Nakamura H, Isaka Y, Yamato M, Hori M.
    Journal: Kidney Int; 2004 Jan; 65(1):15-24. PubMed ID: 14675032.
    Abstract:
    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 micromol/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.
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