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Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction

 Hoon Young Choi  ;  Hyun Gyu Lee  ;  Beom Seok Kim  ;  Sun Hee Ahn  ;  Ara Jung  ;  Mirae Lee  ;  Jung Eun Lee  ;  Hyung Jong Kim  ;  Sung Kyu Ha  ;  Hyeong Cheon Park 
 STEM CELL RESEARCH & THERAPY, Vol.6 : 18, 2015 
Journal Title
Issue Date
Actins/metabolism ; Animals ; Antigens, Differentiation/metabolism ; Cell Line ; Cell Proliferation ; Cell-Derived Microparticles/metabolism* ; Coculture Techniques ; Disease Models, Animal ; Epithelial-Mesenchymal Transition/physiology* ; Fibrosis/pathology ; Fibrosis/therapy ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Inflammation/pathology ; Kidney Tubules/pathology ; Mesenchymal Stromal Cells/metabolism* ; Mice ; Nephritis, Interstitial/therapy ; Transforming Growth Factor beta/pharmacology ; Ureteral Obstruction/pathology ; Ureteral Obstruction/therapy*
INTRODUCTION: Microparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo.
METHODS: MPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson's trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining.
RESULTS: KMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson's trichrome staining, respectively.
CONCLUSIONS: Our results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Park, Hyeong Cheon(박형천) ORCID logo https://orcid.org/0000-0002-1550-0812
Lee, Mi Rae(이미래)
Lee, Jung Eun(이정은) ORCID logo https://orcid.org/0000-0003-0917-2872
Lee, Hyun Gyu(이현규)
Jung, A Ra(정아라)
Choi, Hoon Young(최훈영) ORCID logo https://orcid.org/0000-0002-4245-0339
Ha, Sung Kyu(하성규)
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