| Full text | |
| Author(s): |
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
Total Authors: 9
|
| Document type: | Journal article |
| Source: | STEM CELLS TRANSLATIONAL MEDICINE; v. 5, n. 8, p. 1048-1057, AUG 2016. |
| Web of Science Citations: | 13 |
| Abstract | |
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) | |
| FAPESP's process: | 13/09179-3 - Evaluation of mesenchymal stem cells from human umbilical cord on organ damage and endothelial dysfunction in sepsis |
| Grantee: | José Manuel Cóndor Capcha |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 10/19012-0 - Evaluation of hematopoietic stem cell treatment in dogs with chronic renal failure |
| Grantee: | Lucia da Conceição Andrade |
| Support Opportunities: | Research Projects - Thematic Grants |