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Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation
Mesenchymal stem cells (MSCs) have been shown to improve the outcome of acute renal injury models; but whether MSCs 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 f...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393722/ https://www.ncbi.nlm.nih.gov/pubmed/22862802 http://dx.doi.org/10.1111/j.1582-4934.2012.01610.x |
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author | Chang, Jei-Wen Tsai, Hsin-Lin Chen, Chang-Wei Yang, Hui-Wen Yang, An-Hang Yang, Ling-Yu Wang, Paulus S Ng, Yee-Yung Lin, Teng-Lung Lee, Oscar K |
author_facet | Chang, Jei-Wen Tsai, Hsin-Lin Chen, Chang-Wei Yang, Hui-Wen Yang, An-Hang Yang, Ling-Yu Wang, Paulus S Ng, Yee-Yung Lin, Teng-Lung Lee, Oscar K |
author_sort | Chang, Jei-Wen |
collection | PubMed |
description | Mesenchymal stem cells (MSCs) have been shown to improve the outcome of acute renal injury models; but whether MSCs 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 MSCs in the absence or presence of ascorbic acid 2-phosphate to quantify the protective effects of conditioned MSCs on renal cells. Moreover, male Sprague-Dawley rats were treated with 1 × 10(6) conditioned MSCs 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 MSCs. Besides, conditioned MSCs were found to be protective against TGF-β1 induced epithelial-to-mesenchymal transition of NRK-52E and activation of NRK-49F cells. Furthermore, conditioned MSCs protected podocytes from TGF-β1-induced loss of synaptopodin, fibronectin induction, cell death and apoptosis. Rats transplanted with conditioned human MSCs had a significantly increase in creatinine clearance rate, decrease in glomerulosclerosis, interstitial fibrosis and increase in CD4(+)CD25(+)Foxp3(+) regulatory T cells counts in splenocytes. Together, our studies indicated that conditioned MSCs preserve renal function by their anti-fibrotic and anti-inflammatory effects. Transplantation of conditioned MSCs may be useful in treating CKD. |
format | Online Article Text |
id | pubmed-4393722 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43937222015-04-13 Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation Chang, Jei-Wen Tsai, Hsin-Lin Chen, Chang-Wei Yang, Hui-Wen Yang, An-Hang Yang, Ling-Yu Wang, Paulus S Ng, Yee-Yung Lin, Teng-Lung Lee, Oscar K J Cell Mol Med Original Articles Mesenchymal stem cells (MSCs) have been shown to improve the outcome of acute renal injury models; but whether MSCs 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 MSCs in the absence or presence of ascorbic acid 2-phosphate to quantify the protective effects of conditioned MSCs on renal cells. Moreover, male Sprague-Dawley rats were treated with 1 × 10(6) conditioned MSCs 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 MSCs. Besides, conditioned MSCs were found to be protective against TGF-β1 induced epithelial-to-mesenchymal transition of NRK-52E and activation of NRK-49F cells. Furthermore, conditioned MSCs protected podocytes from TGF-β1-induced loss of synaptopodin, fibronectin induction, cell death and apoptosis. Rats transplanted with conditioned human MSCs had a significantly increase in creatinine clearance rate, decrease in glomerulosclerosis, interstitial fibrosis and increase in CD4(+)CD25(+)Foxp3(+) regulatory T cells counts in splenocytes. Together, our studies indicated that conditioned MSCs preserve renal function by their anti-fibrotic and anti-inflammatory effects. Transplantation of conditioned MSCs may be useful in treating CKD. BlackWell Publishing Ltd 2012-12 2012-12-13 /pmc/articles/PMC4393722/ /pubmed/22862802 http://dx.doi.org/10.1111/j.1582-4934.2012.01610.x Text en © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd |
spellingShingle | Original Articles Chang, Jei-Wen Tsai, Hsin-Lin Chen, Chang-Wei Yang, Hui-Wen Yang, An-Hang Yang, Ling-Yu Wang, Paulus S Ng, Yee-Yung Lin, Teng-Lung Lee, Oscar K Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation |
title | Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation |
title_full | Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation |
title_fullStr | Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation |
title_full_unstemmed | Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation |
title_short | Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation |
title_sort | conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393722/ https://www.ncbi.nlm.nih.gov/pubmed/22862802 http://dx.doi.org/10.1111/j.1582-4934.2012.01610.x |
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