Synergic Renoprotective Effects of Combined ASC Therapy with RAAS Blockade in Experimental Advanced CKD

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorMAIRES, Marina P. C.
dc.contributor.authorPEREIRA, Krislley R.
dc.contributor.authorSILVA, Everidiene K. V. B.
dc.contributor.authorSOUZA, Victor H. R.
dc.contributor.authorTELES, Flavio
dc.contributor.authorBARBOSA, Paulyana F.
dc.contributor.authorGARNICA, Margoth R.
dc.contributor.authorORNELLAS, Felipe M.
dc.contributor.authorNORONHA, Irene L.
dc.contributor.authorFANELLI, Camilla
dc.date.accessioned2022-08-12T17:03:41Z
dc.date.available2022-08-12T17:03:41Z
dc.date.issued2022
dc.description.abstractGlobal prevalence of chronic kidney disease (CKD) has increased considerably in the recent decades. Overactivity of the renin-angiotensin-aldosterone system (RAAS), associated to renal inflammation and fibrosis, contributes to its evolution. The treatments currently employed to control CKD progression are limited and mainly based on the pharmacological inhibition of RAAS, associated with diuretics and immunosuppressive drugs. However, this conservative management promotes only partial deceleration of CKD evolution and does not completely avoid the progression of the disease and the loss of renal function, which motivates the medical and scientific community to investigate new therapeutic approaches to detain renal inflammation/fibrosis and CKD progression. Recent studies have shown the application of mesenchymal stem cells (mSC) to exert beneficial effects on the renal tissue of animals submitted to experimental models of CKD. In this context, the aim of the present study was to evaluate the effects of subcapsular application of adipose tissue-derived mSC (ASC) in rats submitted to the 5/6 renal ablation model, 15 days after the establishment of CKD, when the nephropathy was already severe. We also verify whether ASC associated to Losartan would promote greater renoprotection when compared to the respective monotherapies. Animals were followed until 30 days of CKD, when body weight, systolic blood pressure, biochemical, histological, immunohistochemical, and gene expression analysis were performed. The combination of ASC and Losartan was more effective than Losartan monotherapy in reducing systolic blood pressure and glomerulosclerosis and also promoted the complete normalization of proteinuria and albuminuria, a significant reduction in renal interstitial macrophage infiltration and downregulation of renal IL-6 gene expression. The beneficial effects of ACS are possibly due to the immunomodulatory and anti-inflammatory role of factors secreted by these cells, modulating the local immune response. Although studies are still required, our results demonstrated that a subcapsular inoculation of ASC, associated with the administration of Losartan, exerted additional renoprotective effect in rats submitted to a severe model of established CKD, when compared to Losartan monotherapy, thus suggesting ASC may be a potential adjuvant to RAAS-blockade therapy currently employed in the conservative management of CKD.eng
dc.description.indexPubMedeng
dc.description.sponsorshipSao Paulo Research Foundation [2017/26216-0]
dc.identifier.citationSTEM CELLS INTERNATIONAL, v.2022, article ID 5111782, 20p, 2022
dc.identifier.doi10.1155/2022/5111782
dc.identifier.eissn1687-9678
dc.identifier.issn1687-966X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/48286
dc.language.isoeng
dc.publisherHINDAWI LTDeng
dc.relation.ispartofStem Cells International
dc.rightsopenAccesseng
dc.rights.holderCopyright HINDAWI LTDeng
dc.subject.otherangiotensin-iieng
dc.subject.otherrenal-diseaseeng
dc.subject.othercellseng
dc.subject.otherprogressioneng
dc.subject.otherfibrosiseng
dc.subject.wosCell & Tissue Engineeringeng
dc.titleSynergic Renoprotective Effects of Combined ASC Therapy with RAAS Blockade in Experimental Advanced CKDeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalPEREIRA, Krislley R.:Univ Sao Paulo, Fac Med, Renal Div, Lab Cellular Genet & Mol Nephrol, Sao Paulo, Brazil
hcfmusp.author.externalTELES, Flavio:State Univ Hlth Sci, Fac Med, Dept Clin Med, Renal Div, Maceio, Alagoas, Brazil
hcfmusp.author.externalBARBOSA, Paulyana F.:State Univ Hlth Sci, Fac Med, Dept Clin Med, Renal Div, Maceio, Alagoas, Brazil
hcfmusp.citation.scopus2
hcfmusp.contributor.author-fmusphcMARINA PEREIRA CLARO MAIRES
hcfmusp.contributor.author-fmusphcEVERIDIENE KINVERLLY VIEIRA BORGES DA SILVA
hcfmusp.contributor.author-fmusphcVICTOR HUGO RODRIGUES DE SOUZA
hcfmusp.contributor.author-fmusphcMARGOTH RAMOS GARNICA
hcfmusp.contributor.author-fmusphcFELIPE MATEUS DOS SANTOS ORNELLAS
hcfmusp.contributor.author-fmusphcIRENE DE LOURDES NORONHA
hcfmusp.contributor.author-fmusphcCAMILLA FANELLI
hcfmusp.description.articlenumber5111782
hcfmusp.description.volume2022
hcfmusp.origemWOS
hcfmusp.origem.pubmed35371263
hcfmusp.origem.scopus2-s2.0-85128365086
hcfmusp.origem.wosWOS:000813166600001
hcfmusp.publisher.cityLONDONeng
hcfmusp.publisher.countryENGLANDeng
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