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Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway

Objective: Because the poor survival of transplanted cells in a hostile microenvironment limits stem cell therapy, in the current study, we investigated the effect of rapamycin (Rapa)-preactivated autophagy on the survival and homing of transplanted adipose mesenchymal stem cells (ADMSCs) in a rat m...

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Autores principales: Awadalla, Amira, Hussein, Abdelaziz M., El-Far, Yousra M., El-Senduny, Fardous F., Barakat, Nashwa, Hamam, Eman T., Abdeen, Hanaa M., El-Sherbiny, Mohamed, Serria, Mohamed S., Sarhan, Amira A., Sena, Asmaa M., Shokeir, Ahmed A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220220/
https://www.ncbi.nlm.nih.gov/pubmed/35740317
http://dx.doi.org/10.3390/biomedicines10061295
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author Awadalla, Amira
Hussein, Abdelaziz M.
El-Far, Yousra M.
El-Senduny, Fardous F.
Barakat, Nashwa
Hamam, Eman T.
Abdeen, Hanaa M.
El-Sherbiny, Mohamed
Serria, Mohamed S.
Sarhan, Amira A.
Sena, Asmaa M.
Shokeir, Ahmed A.
author_facet Awadalla, Amira
Hussein, Abdelaziz M.
El-Far, Yousra M.
El-Senduny, Fardous F.
Barakat, Nashwa
Hamam, Eman T.
Abdeen, Hanaa M.
El-Sherbiny, Mohamed
Serria, Mohamed S.
Sarhan, Amira A.
Sena, Asmaa M.
Shokeir, Ahmed A.
author_sort Awadalla, Amira
collection PubMed
description Objective: Because the poor survival of transplanted cells in a hostile microenvironment limits stem cell therapy, in the current study, we investigated the effect of rapamycin (Rapa)-preactivated autophagy on the survival and homing of transplanted adipose mesenchymal stem cells (ADMSCs) in a rat model of cisplatin (Cis)-induced nephrotoxicity, as well as the possible role of the mTOR/AKT signaling pathway. Materials and methods: In vitro, ADMSCs isolated from rats were treated with 50 nmol/L rapamycin for 2 h, after which the cytoprotective and autophagy-inducing effects of Rapa were investigated. The cis-induced acute nephrotoxicity rat model was constructed in vivo. ADMSCs and Rapa-ADMSCs were administered into the tail vein before Cis therapy. At 3, 7, and 10 days after Cis injection, all animals were euthanized. The renal functions and morphology as well as autophagy response were assessed. Results: The pretreatment of cultured ADMSCs with Rapa caused a significant increase in autophagic activities and lysosome production of the cells, with a significant increase in the secretion of SDF-1, IL-10 and autophagy promoter LC3 and Beclin from these cells, while mTOR/AKT pathways were inhibited. In addition, the transplantation of Rapa-pretreated ADMSCs restored the kidney functions and morphology dramatically. Renal expression of SDF-1 and HIF1 was upregulated, while expression of IL-6, NF-kB and TGF-β1 was downregulated. Conclusions: We concluded that the preactivation of autophagy with Rapa improves the survival and differentiation of the transplanted ADMSCs by inhibiting the mTOR/AKT signaling pathway, which in turn could significantly attenuate the Cis-induced acute renal injury.
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spelling pubmed-92202202022-06-24 Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway Awadalla, Amira Hussein, Abdelaziz M. El-Far, Yousra M. El-Senduny, Fardous F. Barakat, Nashwa Hamam, Eman T. Abdeen, Hanaa M. El-Sherbiny, Mohamed Serria, Mohamed S. Sarhan, Amira A. Sena, Asmaa M. Shokeir, Ahmed A. Biomedicines Article Objective: Because the poor survival of transplanted cells in a hostile microenvironment limits stem cell therapy, in the current study, we investigated the effect of rapamycin (Rapa)-preactivated autophagy on the survival and homing of transplanted adipose mesenchymal stem cells (ADMSCs) in a rat model of cisplatin (Cis)-induced nephrotoxicity, as well as the possible role of the mTOR/AKT signaling pathway. Materials and methods: In vitro, ADMSCs isolated from rats were treated with 50 nmol/L rapamycin for 2 h, after which the cytoprotective and autophagy-inducing effects of Rapa were investigated. The cis-induced acute nephrotoxicity rat model was constructed in vivo. ADMSCs and Rapa-ADMSCs were administered into the tail vein before Cis therapy. At 3, 7, and 10 days after Cis injection, all animals were euthanized. The renal functions and morphology as well as autophagy response were assessed. Results: The pretreatment of cultured ADMSCs with Rapa caused a significant increase in autophagic activities and lysosome production of the cells, with a significant increase in the secretion of SDF-1, IL-10 and autophagy promoter LC3 and Beclin from these cells, while mTOR/AKT pathways were inhibited. In addition, the transplantation of Rapa-pretreated ADMSCs restored the kidney functions and morphology dramatically. Renal expression of SDF-1 and HIF1 was upregulated, while expression of IL-6, NF-kB and TGF-β1 was downregulated. Conclusions: We concluded that the preactivation of autophagy with Rapa improves the survival and differentiation of the transplanted ADMSCs by inhibiting the mTOR/AKT signaling pathway, which in turn could significantly attenuate the Cis-induced acute renal injury. MDPI 2022-05-31 /pmc/articles/PMC9220220/ /pubmed/35740317 http://dx.doi.org/10.3390/biomedicines10061295 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Awadalla, Amira
Hussein, Abdelaziz M.
El-Far, Yousra M.
El-Senduny, Fardous F.
Barakat, Nashwa
Hamam, Eman T.
Abdeen, Hanaa M.
El-Sherbiny, Mohamed
Serria, Mohamed S.
Sarhan, Amira A.
Sena, Asmaa M.
Shokeir, Ahmed A.
Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
title Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
title_full Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
title_fullStr Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
title_full_unstemmed Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
title_short Rapamycin Improves Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Renoprotective Effect against Cisplatin-Induced Acute Nephrotoxicity in Rats by Inhibiting the mTOR/AKT Signaling Pathway
title_sort rapamycin improves adipose-derived mesenchymal stem cells (admscs) renoprotective effect against cisplatin-induced acute nephrotoxicity in rats by inhibiting the mtor/akt signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220220/
https://www.ncbi.nlm.nih.gov/pubmed/35740317
http://dx.doi.org/10.3390/biomedicines10061295
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