| RRC ID |
56640
|
| 著者 |
Yoshida K, Nakashima A, Doi S, Ueno T, Okubo T, Kawano KI, Kanawa M, Kato Y, Higashi Y, Masaki T.
|
| タイトル |
Serum-Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis.
|
| ジャーナル |
Stem Cells Transl Med
|
| Abstract |
Serum used in culture medium brings risks of immune reactions or infections and thus may hinder using ex vivo expanded mesenchymal stem cells (MSCs) for medical treatment. Here, we cultured MSCs in a serum-free medium (SF-MSCs) and in a medium containing 10% fetal bovine serum (10%MSCs) and investigated their effects on inflammation and fibrosis. MSC-conditioned medium suppressed transforming growth factor-β1-induced phosphorylation of Smad2 in HK-2 cells, with no significant difference between the two MSCs. This finding suggests that the direct antifibrotic effect of SF-MSCs is similar to that of 10%MSCs. However, immunohistochemistry revealed that renal fibrosis induced by unilateral ureteral obstruction in rats was more significantly ameliorated by the administration of SF-MSCs than by that of 10%MSCs. Coculture of MSCs and monocytic THP-1 cell-derived macrophages using a Transwell system showed that SF-MSCs significantly induced polarization from the proinflammatory M1 to the immunosuppressive M2 phenotype macrophages, suggesting that SF-MSCs strongly suppress the persistence of inflammation. Furthermore, the gene expression of tumor necrosis factor-α-induced protein 6 (TSG-6), which inhibits the recruitment of inflammatory cells, was higher in SF-MSCs than in 10%MSCs, and TSG-6 knockdown in SF-MSCs attenuated the anti-inflammatory responses in unilateral ureteral obstruction rats. These findings imply that SF culture conditions can enhance the immunosuppressive and antifibrotic abilities of MSCs and the administration of ex vivo expanded SF-MSCs has the potential to be a useful therapy for preventing the progression of renal fibrosis. Stem Cells Translational Medicine 2018;7:893-905.
|
| 巻・号 |
7(12)
|
| ページ |
893-905
|
| 公開日 |
2018-12-1
|
| DOI |
10.1002/sctm.17-0284
|
| PMID |
30269426
|
| PMC |
PMC6265641
|
| MeSH |
Animals
Antigens, CD / metabolism
Antigens, Differentiation, Myelomonocytic / metabolism
Cell Adhesion Molecules / antagonists & inhibitors
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism
Coculture Techniques
Collagen Type I / genetics
Collagen Type I / metabolism
Culture Media, Serum-Free / chemistry
Culture Media, Serum-Free / pharmacology
Fibrosis
Kidney Diseases / etiology
Kidney Diseases / pathology
Kidney Diseases / therapy*
Macrophages / cytology
Macrophages / immunology
Macrophages / metabolism
Male
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / drug effects
Mesenchymal Stem Cells / metabolism*
Models, Animal
RNA Interference
RNA, Small Interfering / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Cell Surface / metabolism
Smad2 Protein / metabolism
Ureteral Obstruction / complications
Ureteral Obstruction / pathology
|
| IF |
5.962
|
| 引用数 |
7
|
| リソース情報 |
| ヒト・動物細胞 |
THP-1(RCB1189)
Human mesenchymal stem cells |
