Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization
Purpose. Recent evidence has shown that CD4+ T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4+ T cells remains unknown. Our research investigated the effects of intravenously administered...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2020-01-01
|
Series: | Stem Cells International |
Online Access: | http://dx.doi.org/10.1155/2020/2685820 |
id |
doaj-dd3322f39f1546338a88ff4b32c6fdc7 |
---|---|
record_format |
Article |
spelling |
doaj-dd3322f39f1546338a88ff4b32c6fdc72020-11-25T02:53:11ZengHindawi LimitedStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/26858202685820Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell PolarizationZhu Zhu0Chaonan Han1Shuli Xian2Feng Zhuang3Feng Ding4Wei Zhang5Yingli Liu6Department of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDepartment of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaPurpose. Recent evidence has shown that CD4+ T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4+ T cells remains unknown. Our research investigated the effects of intravenously administered placenta mesenchymal stromal cells (PMSCs) or treatment with extracellular EVs (EVs) derived from PMSCs (PMSC-EVs) on the polarization of CD4+ T cells in rats with unilateral ureteral obstruction (UUO). We further verified how PMSCs affect inflammatory factor secretion and the levels of regulatory T (Treg) and Th17 CD4+ T cells in vitro. Materials and Methods. We evaluated renal interstitial inflammation and fibrosis by pathological section staining, tested the polarization of CD4+ T cells (Th17 and Treg phenotypes) by flow cytometry (FCM) and immunohistochemistry, and detected the cytokines secreted by CD4+ T cells by enzyme-linked immunosorbent assay (ELISA). Results. Compared with that of control rats, the renal tissue of PMSC-treated rats exhibited lower renal Masson scores and more Foxp3+ cell infiltration, with a significantly decreased IL17A+CD4+ T cell/CD4+ T cell ratio and a significantly elevated anti-inflammatory cytokine (IL-10) level. When CD4+ T cells were cocultured with PMSCs, CD4+IL17A+ cell percentages were decreased in a UUO model after 7 days of coculture with PMSCs. The secretion of TGF-β and IL-10 was significantly increased (P<0.05), while the secretion of IFN-γ, IL-17, and IL-6 was significantly decreased (P<0.05) in the PMSC coculture group. Moreover, after treatment with PMSC-EVs, tubulointerstitial fibrosis was alleviated, and Foxp3+/IL-17+ cell infiltration was increased in the kidneys of UUO model animals on day 7. Conclusions. PMSCs can convert the inflammatory environment into an anti-inflammatory environment by affecting the polarization of CD4+ T cells and macrophages, inhibiting the inflammatory factors IFN-γ and IL-17, and upregulating the expression of the anti-inflammatory factors TGF-β and IL-10, ultimately leading to renal protection. Such functions may be mediated by the paracrine activity of PMSC-EVs.http://dx.doi.org/10.1155/2020/2685820 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhu Zhu Chaonan Han Shuli Xian Feng Zhuang Feng Ding Wei Zhang Yingli Liu |
spellingShingle |
Zhu Zhu Chaonan Han Shuli Xian Feng Zhuang Feng Ding Wei Zhang Yingli Liu Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization Stem Cells International |
author_facet |
Zhu Zhu Chaonan Han Shuli Xian Feng Zhuang Feng Ding Wei Zhang Yingli Liu |
author_sort |
Zhu Zhu |
title |
Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization |
title_short |
Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization |
title_full |
Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization |
title_fullStr |
Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization |
title_full_unstemmed |
Placental Mesenchymal Stromal Cells (PMSCs) and PMSC-Derived Extracellular Vesicles (PMSC-EVs) Attenuated Renal Fibrosis in Rats with Unilateral Ureteral Obstruction (UUO) by Regulating CD4+ T Cell Polarization |
title_sort |
placental mesenchymal stromal cells (pmscs) and pmsc-derived extracellular vesicles (pmsc-evs) attenuated renal fibrosis in rats with unilateral ureteral obstruction (uuo) by regulating cd4+ t cell polarization |
publisher |
Hindawi Limited |
series |
Stem Cells International |
issn |
1687-966X 1687-9678 |
publishDate |
2020-01-01 |
description |
Purpose. Recent evidence has shown that CD4+ T helper (Th) cells are involved in renal inflammation and fibrosis. However, whether renal fibrosis can be alleviated by intervening in the polarization of CD4+ T cells remains unknown. Our research investigated the effects of intravenously administered placenta mesenchymal stromal cells (PMSCs) or treatment with extracellular EVs (EVs) derived from PMSCs (PMSC-EVs) on the polarization of CD4+ T cells in rats with unilateral ureteral obstruction (UUO). We further verified how PMSCs affect inflammatory factor secretion and the levels of regulatory T (Treg) and Th17 CD4+ T cells in vitro. Materials and Methods. We evaluated renal interstitial inflammation and fibrosis by pathological section staining, tested the polarization of CD4+ T cells (Th17 and Treg phenotypes) by flow cytometry (FCM) and immunohistochemistry, and detected the cytokines secreted by CD4+ T cells by enzyme-linked immunosorbent assay (ELISA). Results. Compared with that of control rats, the renal tissue of PMSC-treated rats exhibited lower renal Masson scores and more Foxp3+ cell infiltration, with a significantly decreased IL17A+CD4+ T cell/CD4+ T cell ratio and a significantly elevated anti-inflammatory cytokine (IL-10) level. When CD4+ T cells were cocultured with PMSCs, CD4+IL17A+ cell percentages were decreased in a UUO model after 7 days of coculture with PMSCs. The secretion of TGF-β and IL-10 was significantly increased (P<0.05), while the secretion of IFN-γ, IL-17, and IL-6 was significantly decreased (P<0.05) in the PMSC coculture group. Moreover, after treatment with PMSC-EVs, tubulointerstitial fibrosis was alleviated, and Foxp3+/IL-17+ cell infiltration was increased in the kidneys of UUO model animals on day 7. Conclusions. PMSCs can convert the inflammatory environment into an anti-inflammatory environment by affecting the polarization of CD4+ T cells and macrophages, inhibiting the inflammatory factors IFN-γ and IL-17, and upregulating the expression of the anti-inflammatory factors TGF-β and IL-10, ultimately leading to renal protection. Such functions may be mediated by the paracrine activity of PMSC-EVs. |
url |
http://dx.doi.org/10.1155/2020/2685820 |
work_keys_str_mv |
AT zhuzhu placentalmesenchymalstromalcellspmscsandpmscderivedextracellularvesiclespmscevsattenuatedrenalfibrosisinratswithunilateralureteralobstructionuuobyregulatingcd4tcellpolarization AT chaonanhan placentalmesenchymalstromalcellspmscsandpmscderivedextracellularvesiclespmscevsattenuatedrenalfibrosisinratswithunilateralureteralobstructionuuobyregulatingcd4tcellpolarization AT shulixian placentalmesenchymalstromalcellspmscsandpmscderivedextracellularvesiclespmscevsattenuatedrenalfibrosisinratswithunilateralureteralobstructionuuobyregulatingcd4tcellpolarization AT fengzhuang placentalmesenchymalstromalcellspmscsandpmscderivedextracellularvesiclespmscevsattenuatedrenalfibrosisinratswithunilateralureteralobstructionuuobyregulatingcd4tcellpolarization AT fengding placentalmesenchymalstromalcellspmscsandpmscderivedextracellularvesiclespmscevsattenuatedrenalfibrosisinratswithunilateralureteralobstructionuuobyregulatingcd4tcellpolarization AT weizhang placentalmesenchymalstromalcellspmscsandpmscderivedextracellularvesiclespmscevsattenuatedrenalfibrosisinratswithunilateralureteralobstructionuuobyregulatingcd4tcellpolarization AT yingliliu placentalmesenchymalstromalcellspmscsandpmscderivedextracellularvesiclespmscevsattenuatedrenalfibrosisinratswithunilateralureteralobstructionuuobyregulatingcd4tcellpolarization |
_version_ |
1715359856618110976 |