Treatment With Human Wharton's Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction

Autor(es)

Condor, Jose M. ; Rodrigues, Camila E. ; Moreira, Roberto de Sousa ; Canale, Daniele ; Volpini, Rildo A. ; Shimizu, Maria H. M. ; Camara, Niels O. S. ; Noronha, Irene de L. ; Andrade, Lucia

• Tipo de documento: Artigo Científico
• Fonte: STEM CELLS TRANSLATIONAL MEDICINE; v. 5, n. 8, p. 1048-1057, AUG 2016.
• Citações Web of Science: 13

Resumo

The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and rats submitted to CLP and intraperitoneally injected, 6 hours later, with 1 x 10(6) WJ-MSCs. The glomerular filtration rate (GFR) was measured at 6 and 24 hours after CLP or sham surgery. All other studies were conducted at 24 hours after CLP or sham surgery. By 6 hours, GFR had decreased in the CLP rats. At 24 hours, Klotho renal expression significantly decreased. Treatment with WJ-MSCs improved the GFR; improved tubular function; decreased the CD68-positive cell count; decreased the fractional interstitial area; decreased expression of nuclear factor kappa B and of cytokines; increased expression of eNOS, vascular endothelial growth factor, and Klotho; attenuated renal apoptosis; ameliorated hepatic function; increased glycogen deposition in the liver; and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. Klotho protein expression was higher in WJ-MSCs than in human adipose-derived MSCs. Because WJ-MSCs preserve renal and hepatic function, they might play a protective role in sepsis. SIGNIFICANCE Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor kappa B and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. (AU)

• Processo FAPESP: 13/09179-3 - Avaliação de células-tronco mesenquimais de cordão umbilical humano em lesão de órgãos e a disfunção endotelial na sepse
• Beneficiário: José Manuel Cóndor Capcha
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 10/19012-0 - Avaliação da terapia com células-tronco hematopoiéticas na doença renal crônica em cães
• Beneficiário: Lucia da Conceição Andrade
• Modalidade de apoio: Auxílio à Pesquisa - Temático