Format

Send to

Choose Destination
Stem Cell Res Ther. 2015 Mar 11;6:18. doi: 10.1186/s13287-015-0012-6.

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

Author information

1
Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. hychoi.dr@gmail.com.
2
Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea. hychoi.dr@gmail.com.
3
Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, Korea. HLEE23@yuhs.ac.
4
Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. docbsk@yuhs.ac.
5
Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. dkwlxm@hanmail.net.
6
Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. eeyorelove@hanmail.net.
7
Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. alfo0103@naver.com.
8
Department of Internal Medicine, Yong-In Severance Hospital, Gyeongi-do, Korea. SW0615@yuhs.ac.
9
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Gyeongi-do, Korea. khj04@cha.ac.kr.
10
Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. hask1951@yuhs.ac.
11
Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. amp97@yuhs.ac.
12
Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea. amp97@yuhs.ac.

Abstract

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.

PMID:
25889661
PMCID:
PMC4393614
DOI:
10.1186/s13287-015-0012-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center