TREATMENT WITH HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN A PIG MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY: EFFECTS ON MICROVASCULAR ENDOTHELIAL CELLS AND TUBULAR CELLS IN THE KIDNEY
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Citações na Scopus
2
Tipo de produção
article
Data de publicação
2023
Título da Revista
ISSN da Revista
Título do Volume
Editora
LIPPINCOTT WILLIAMS & WILKINS
Citação
SHOCK, v.60, n.3, p.469-477, 2023
Resumo
Background: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 x 106 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappa B) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-kappa B signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.
Palavras-chave
Septic shock, acute kidney injury, endothelial protein, stem cell
Referências
- Chang CL, 2018, AM J TRANSL RES, V10, P1053
- Chertow GM, 2005, J AM SOC NEPHROL, V16, P3365, DOI 10.1681/ASN.2004090740
- Cóndor JM, 2016, STEM CELL TRANSL MED, V5, P1048, DOI 10.5966/sctm.2015-0138
- Doi K, 2010, CURR VASC PHARMACOL, V8, P122, DOI 10.2174/157016110790226606
- Doi K, 2009, J AM SOC NEPHROL, V20, P1217, DOI 10.1681/ASN.2008060617
- Evans CE, 2017, AM J PHYSIOL-LUNG C, V312, pL441, DOI 10.1152/ajplung.00441.2016
- Fazekas B, 2022, STEM CELL REV REP, V18, P1444, DOI 10.1007/s12015-021-10323-7
- Fazekas B, 2020, KIDNEY INT, V97, P1130, DOI 10.1016/j.kint.2019.12.019
- Gómez H, 2016, CURR OPIN CRIT CARE, V22, P546, DOI 10.1097/MCC.0000000000000356
- Hauschildt J, 2020, J VASC RES, V57, P34, DOI 10.1159/000503787
- Hepokoski M, 2017, AM J PHYSIOL-RENAL, V312, pF654, DOI 10.1152/ajprenal.00523.2016
- Hildebrand F, 2005, EXP TOXICOL PATHOL, V56, P281, DOI 10.1016/j.etp.2004.09.004
- Horak J, 2020, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.00126
- Hoseinnia S, 2021, J CELL BIOCHEM, V122, P1791, DOI 10.1002/jcb.30133
- Iguchi N, 2019, AM J PHYSIOL-REG I, V317, pR232, DOI 10.1152/ajpregu.00371.2018
- Jeong SJ, 2013, CRIT CARE, V17, DOI 10.1186/cc12742
- Kosaka J, 2016, CRIT CARE MED, V44, pE897, DOI 10.1097/CCM.0000000000001735
- Langenberg C, 2008, CRIT CARE, V12, DOI 10.1186/cc6863
- Laroye C, 2018, INTENS CARE MED EXP, V6, DOI 10.1186/s40635-018-0194-1
- Li S, 2018, OXID MED CELL LONGEV, V2018, DOI 10.1155/2018/3537609
- Liu ZJ, 2016, PLOS ONE, V11, DOI 10.1371/journal.pone.0154053
- Luo CJ, 2014, SHOCK, V41, P123, DOI 10.1097/SHK.0000000000000080
- Luo TH, 2013, J TRAUMA ACUTE CARE, V74, P508, DOI 10.1097/TA.0b013e3182703420
- Ma S, 2019, MICROCIRCULATION, V26, DOI 10.1111/micc.12483
- Molema G, 2022, NAT REV NEPHROL, V18, P95, DOI 10.1038/s41581-021-00489-1
- Molteni M, 2016, MEDIAT INFLAMM, V2016, DOI 10.1155/2016/6978936
- Riedemann NC, 2003, J CLIN INVEST, V112, P460, DOI 10.1172/JCI200319523
- Rodrigues CE, 2017, STEM CELL RES THER, V8, DOI 10.1186/s13287-017-0475-8
- Schmidt C, 2007, J AM SOC NEPHROL, V18, P1072, DOI 10.1681/ASN.2006050454
- Tenzi J, 2022, J CRIT CARE, V68, P38, DOI 10.1016/j.jcrc.2021.11.013
- Terblanche M, 2012, CRIT CARE, V16, DOI 10.1186/cc11306
- Xu X, 2015, TRANSPL P, V47, P2991, DOI 10.1016/j.transproceed.2015.10.024
- Zaki OS, 2018, INFLAMMATION, V41, P541, DOI 10.1007/s10753-017-0710-6
- Zarjou A, 2011, J AM SOC NEPHROL, V22, P999, DOI 10.1681/ASN.2010050484
- Zhou Y, 2018, MOL THER, V26, P1375, DOI 10.1016/j.ymthe.2018.02.020
- Zullo JA, 2015, STEM CELL TRANSL MED, V4, P852, DOI 10.5966/sctm.2014-0111
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Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - FM/MCG
Artigos e Materiais de Revistas Científicas - HC/ICHC
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Artigos e Materiais de Revistas Científicas - LIM/06
Carregar mais Artigos e Materiais de Revistas Científicas - FM/MCG
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - LIM/06