Genetic disorders – Development

Kidney International (2004) 65, 15–24; doi:10.1111/j.1523-1755.2004.00379.x

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

AKIRA SUZUKI1, HIROTSUGU IWATANI1, TAKAHITO ITO, ENYU IMAI, MASARU OKABE, HIROYUKI NAKAMURA, YOSHITAKA ISAKA, MASAYA YAMATO and MASATSUGU HORI

Department of Internal Medicine and Therapeutics, Osaka University School of Medicine, Suita, Osaka, Japan; Osaka University Genome Information Research Center, Suita, Osaka, Japan

Correspondence: Takahito Ito M.D., Osaka University School of Medicine, Department of Internal Medicine and Therapeutics, Box A8, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail:taka@medone.med.osaka-u.ac.jp

1Akira Suzuki and Hirotsugu Iwatani contributed equally to this study.

Received 14 March 2003; Revised 4 August 2003; Accepted 20 August 2003.

Top

Abstract

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.

Keywords:

stem cell, GFP rat, PDGF, retinoic acid, mesangial cell

Extra navigation

.
ADVERTISEMENT