RRC ID 56640
Author Yoshida K, Nakashima A, Doi S, Ueno T, Okubo T, Kawano KI, Kanawa M, Kato Y, Higashi Y, Masaki T.
Title Serum-Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis.
Journal 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.
Volume 7(12)
Pages 893-905
Published 2018-12
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
Times Cited 7
Human and Animal Cells THP-1(RCB1189) Human mesenchymal stem cells