CAMILA ELEUTERIO RODRIGUES
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais, Hospital das Clínicas, Faculdade de Medicina
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- Wharton's jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation(2020) CAPCHA, Jose Manuel Condor; RODRIGUES, Camila Eleuterio; MOREIRA, Roberto de Souza; SILVEIRA, Marcelo Duarte; DOURADO, Paulo; SANTOS, Fernando dos; IRIGOYEN, Maria Claudia; JENSEN, Leonardo; GARNICA, Margoth Ramos; NORONHA, Irene L.; ANDRADE, Lucia; GOMES, Samirah AbreuSepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton's jellyderived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by alpha 7-nicotinic acetylcholine receptors (alpha 7nAChRs). which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CL.P+WJ-MSCs (1 x 10(6) cells, at 6 h post-CLP); and CLP+methyllycaconifine (MLA)+WJ-MSCs (5 mg/kg body wt, at 53 h post-CLP, and 1 x 10(6) cells, at 6 h post-CLP. respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective alpha 7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated alpha 7nAChR expression, as well as reduced the phospho-STAT3-tototal STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.