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Transforming growth factor-ß1-overexpressing mesenchymal stromal cells induced local tolerance in rat renal ischemia/reperfusion injury.
Cai, Jieru; Jiao, Xiaoyan; Zhao, Shuan; Liang, Yiran; Ning, Yichun; Shi, Yiqin; Fang, Yi; Ding, Xiaoqiang; Yu, Xiaofang.
Afiliación
  • Cai J; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China.
  • Jiao X; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China.
  • Zhao S; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China.
  • Liang Y; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China.
  • Ning Y; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China.
  • Shi Y; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China.
  • Fang Y; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China.
  • Ding X; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China. Elect
  • Yu X; Department of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China; Shanghai Medical Center for Kidney, Shanghai, China; Shanghai Institute of Kidney and Dialysis, Shanghai, China. Elect
Cytotherapy ; 21(5): 535-545, 2019 05.
Article en En | MEDLINE | ID: mdl-30685215
ABSTRACT

BACKGROUND:

Regulatory T cells (Tregs) suppress excessive immune responses and play a crucial protective role in acute kidney injury (AKI). The aim of this study was to examine the therapeutic potential of transforming growth factor (TGF)-ß1-overexpressing mesenchymal stromal cells (MSCs) in inducing local generation of Tregs in the kidney after ischemia/reperfusion (I/R) injury.

METHODS:

MSCs were transduced with a lentiviral vector expressing the TGF-ß1 gene; TGF-ß1-overexpressing MSCs (designated TGF-ß1/MSCs) were then transfused into the I/R-injured kidney via the renal artery.

RESULTS:

MSCs genetically modified with TGF-ß1 achieved overexpression of TGF-ß1. Compared with green fluorescent protein (GFP)/MSCs, TGF-ß1/MSCs markedly improved renal function after I/R injury and reduced epithelial apoptosis and subsequent inflammation. The enhanced immunosuppressive and therapeutic abilities of TGF-ß1/MSCs were associated with increased generation of induced Tregs and improved intrarenal migration of the injected cells. Futhermore, the mechanism of TGF-ß1/MSCs in attenuating renal I/R injury was not through a direct canonical TGF-ß1/Smad pathway.

CONCLUSION:

TGF-ß1/MSCs can induce a local immunosuppressive effect in the I/R-injured kidney. The immunomodulatory activity of TGF-ß1-modified MSCs appears to be a gateway to new therapeutic approaches to prevent renal I/R injury.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Daño por Reperfusión / Trasplante de Células Madre Mesenquimatosas / Factor de Crecimiento Transformador beta1 / Células Madre Mesenquimatosas / Enfermedades Renales Límite: Animals Idioma: En Revista: Cytotherapy Asunto de la revista: TERAPEUTICA Año: 2019 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Daño por Reperfusión / Trasplante de Células Madre Mesenquimatosas / Factor de Crecimiento Transformador beta1 / Células Madre Mesenquimatosas / Enfermedades Renales Límite: Animals Idioma: En Revista: Cytotherapy Asunto de la revista: TERAPEUTICA Año: 2019 Tipo del documento: Article País de afiliación: China