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
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Human umbilical cord-derived mesenchymal stromal cells protect against premature renal senescence resulting from oxidative stress in rats with acute kidney injury(2017) RODRIGUES, Camila Eleuterio; CAPCHA, Jose Manuel Condor; BRAGANCA, Ana Carolina de; SANCHES, Talita Rojas; GOUVEIA, Priscila Queiroz; OLIVEIRA, Patricia Aparecida Ferreira de; MALHEIROS, Denise Maria Avancini Costa; VOLPINI, Rildo Aparecido; SANTINHO, Mirela Aparecida Rodrigues; SANTANA, Barbara Amelia Aparecida; CALADO, Rodrigo do Tocantins; NORONHA, Irene de Lourdes; ANDRADE, LuciaBackground: Mesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats. Methods: By clamping both renal arteries for 45 min, we induced IRI in male rats. Six hours later, some rats received 1 x 10(6) huMSCs or human adipose-derived MSCs (aMSCs) intraperitoneally. Rats were euthanised and studied on post-IRI days 2, 7 and 49. Results: On post-IRI day 2, the kidneys of huMSC-treated rats showed improved glomerular filtration, better tubular function and higher expression of aquaporin 2, as well as less macrophage infiltration. Senescence-related proteins (beta-galactosidase, p21Waf1/Cip1, p16INK4a and transforming growth factor beta 1) andmicroRNAs (miR-29a and miR-34a) were overexpressed after IRI and subsequently downregulated by the treatment. The IRI-induced pro-oxidative state and reduction in Klotho expression were both reversed by the treatment. In comparison with huMSC treatment, the treatment with aMSCs improved renal function to a lesser degree, as well as resulting in a less pronounced increase in the renal expression of Klotho and manganese superoxide dismutase. Treatment with huMSCs ameliorated long-term kidney function after IRI, minimised renal fibrosis, decreased beta-galactosidase expression and increased the expression of Klotho. Conclusions: Our data demonstrate that huMSCs attenuate the inflammatory and oxidative stress responses occurring in AKI, as well as reducing the expression of senescence-related proteins and microRNAs. Our findings broaden perspectives for the treatment of AKI.
- Acute Kidney Injury as a Condition of Renal Senescence(2018) ANDRADE, Lucia; RODRIGUES, Camila E.; GOMES, Samirah A.; NORONHA, Irene L.Acute kidney injury (AKI), characterized by a sharp drop in glomerular filtration, continues to be a significant health burden because it is associated with high initial mortality, morbidity, and substantial health-care costs. There is a strong connection between AKI and mechanisms of senescence activation. After ischemic or nephrotoxic insults, a wide range of pathophysiological events occur. Renal tubular cell injury is characterized by cell membrane damage, cytoskeleton disruption, and DNA degradation, leading to tubular cell death by necrosis and apoptosis. The senescence mechanism involves interstitial fibrosis, tubular atrophy, and capillary rarefaction, all of which impede the morphological and functional recovery of the kidneys, suggesting a strong link between AKI and the progression of chronic kidney disease. During abnormal kidney repair, tubular epithelial cells can assume a senescence-like phenotype. Cellular senescence can occur as a result of cell cycle arrest due to increased expression of cyclin kinase inhibitors (mainly p21), downregulation of Klotho expression, and telomere shortening. In AKI, cellular senescence is aggravated by other factors including oxidative stress and autophagy. Given this scenario, the main question is whether AKI can be repaired and how to avoid the senescence process. Stem cells might constitute a new therapeutic approach. Mesenchymal stem cells (MSCs) can ameliorate kidney injury through angiogenesis, immunomodulation, and fibrosis pathway blockade, as well as through antiapoptotic and promitotic processes. Young umbilical cord-derived MSCs are better at increasing Klotho levels, and thus protecting tissues from senescence, than are adipose-derived MSCs. Umbilical cord-derived MSCs improve glomerular filtration and tubular function to a greater degree than do those obtained from adult tissue. Although senescence-related proteins and microRNA are upregulated in AKI, they can be downregulated by treatment with umbilical cord-derived MSCs. In summary, stem cells derived from young tissues, such as umbilical cord-derived MSCs, could slow the post-AKI senescence process.
- 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.
- Endothelial Progenitor Cells in Tumor Angiogenesis: Another Brick in the Wall(2015) MARCOLA, Marina; RODRIGUES, Camila EleuterioUntil 15 years ago, vasculogenesis, the formation of new blood vessels from undifferentiated cells, was thought to occur only during embryonic development. The discovery of circulating cells that are able to promote vascular regeneration and repair-the so-called endothelial progenitor cells (EPCs)-changed that, and EPCs have since been studied extensively. It is already known that EPCs include many subtypes of cells that play a variety of roles in promoting vascular growth. Some EPCs are destined to differentiate into endothelial cells, whereas others are capable of promoting and sustaining angiogenesis through paracrine mechanisms. Vasculogenesis and angiogenesis might constitute complementary mechanisms for postnatal neovascularization, and EPCs could be at the core of this process. Although the formation of new blood vessels from preexisting vasculature plays a beneficial role in many physiological processes, such as wound healing, it also contributes to tumor growth and metastasis. However, many aspects of the role played by EPCs in tumor angiogenesis remain unclear. This review aims to address the main aspects of EPCs differentiation and certain characteristics of their main function, especially in tumor angiogenesis, as well as the potential clinical applications.
- Treatment With Human Wharton's Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction(2016) 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, LuciaThe 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.