Open AccessConditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial‐to‐mesenchymal transition and immune modulation
Author(s) -
Chang JeiWen,
Tsai HsinLin,
Chen ChangWei,
Yang HuiWen,
Yang AnHang,
Yang LingYu,
Wang Paulus S.,
Ng YeeYung,
Lin TengLung,
Lee Oscar K.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01610.x
Subject(s) - hepatocyte growth factor , mesenchymal stem cell , ascorbic acid , medicine , fibrosis , endocrinology , cancer research , chemistry , pathology , receptor , food science
Mesenchymal stem cells ( MSC s) have been shown to improve the outcome of acute renal injury models; but whether MSC s can delay renal failure in chronic kidney disease ( CKD ) remains unclear. In the present study, the were cultured in media containing various concentrations of basic fibroblast growth factor, epidermal growth factor and ascorbic acid 2‐phosphate to investigate whether hepatocyte growth factor ( HGF ) secretion could be increased by the stimulation of these growth factors. Then, TGF ‐β1‐treated renal interstitial fibroblast ( NRK ‐49F), renal proximal tubular cells ( NRK ‐52E) and podocytes were co‐cultured with conditioned MSC s in the absence or presence of ascorbic acid 2‐phosphate to quantify the protective effects of conditioned MSC s on renal cells. Moreover, male Sprague‐Dawley rats were treated with 1 × 10 6 conditioned MSC s immediately after 5/6 nephrectomy and every other week through the tail vein for 14 weeks. It was found that basic fibroblast growth factor, epidermal growth factor and ascorbic acid 2‐phosphate promoted HGF secretion in MSC s. Besides, conditioned MSC s were found to be protective against TGF ‐β1 induced epithelial‐to‐mesenchymal transition of NRK ‐52E and activation of NRK ‐49F cells. Furthermore, conditioned MSC s protected podocytes from TGF ‐β1‐induced loss of synaptopodin, fibronectin induction, cell death and apoptosis. Rats transplanted with conditioned human MSC s had a significantly increase in creatinine clearance rate, decrease in glomerulosclerosis, interstitial fibrosis and increase in CD 4 + CD 25 + Foxp3 + regulatory T cells counts in splenocytes. Together, our studies indicated that conditioned MSC s preserve renal function by their anti‐fibrotic and anti‐inflammatory effects. Transplantation of conditioned MSC s may be useful in treating CKD .