Treatment of murine fulminant hepatitis with genetically engineered endothelial progenitor cells

Fernández-Ruiz, Verónica; Kawa, Miłosz; Berasain, Carmen; Íñiguez, María; Schmitz, Volker; Martı́nez-Ansó, Eduardo; Iñarrairaegui, Mercedes; Herrero, Ignacio; Sangro, Bruno; Avola, Delia D; Quiroga, Jorge; Qian, Cheng; Prieto, Jesús

doi:10.1016/j.jhep.2011.01.036

Cited by 14 publications

(7 citation statements)

References 22 publications

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“…It has been shown that, in addition to hepatocytes, RHDV can also infect endothelial cells and intravascular macrophages by promoting the activation and apoptosis of these cells, which may play a pathogenic role in RHDV-induced ALF (1,27). It has been reported that CT-1 reduces macrophage activation (6) and exerts a protective role on endothelial cells (26). These effects on nonparenchymal cells might also contribute to the attenuation of liver damage observed in the infected animals treated with CT-1.…”

Section: Discussionmentioning

confidence: 99%

Cardiotrophin-1 Promotes a High Survival Rate in Rabbits with Lethal Fulminant Hepatitis of Viral Origin

Tuñón

Miguel

Crespo

et al. 2011

J Virol

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Rabbit hemorrhagic disease virus (RHDV) causes lethal fulminant hepatitis closely resembling acute liver failure (ALF) in humans. In this study, we investigated whether cardiotrophin-1 (CT-1), a cytokine with hepatoprotective properties, could attenuate liver damage and prolong survival in virus-induced ALF. Twentyfour rabbits were infected with 2 ؋ 10 4 hemagglutination units of RHDV. Twelve received five doses of CT-1 (100 g/kg) starting at 12 h postinfection (hpi) (the first three doses every 6 h and then two additional doses at 48 and 72 hpi), while the rest received saline. The animals were analyzed for survival, serum biochemistry, and viral load. Another cohort (n ‫؍‬ 22) was infected and treated similarly, but animals were sacrificed at 30 and 36 hpi to analyze liver histology, viral load, and the expression of factors implicated in liver damage and repair. All infected rabbits that received saline died by 60 hpi, while 67% of the CT-1-treated animals survived until the end of the study. Treated animals showed improved liver function and histology, while the viral loads were similar. In the livers of CT-1-treated rabbits we observed reduction of oxidative stress, diminished PARP1/2 and JNK activation, and decreased inflammatory reaction, as reflected by reduced expression of tumor necrosis factor alpha, interleukin-1␤, Toll-like receptor 4, VCAM-1, and MMP-9. In addition, CT-1-treated rabbits exhibited marked upregulation of TIMP-1 and increased expression of cytoprotective and proregenerative growth factors, including platelet-derived growth factor B, epidermal growth factor, plateletderived growth factor receptor ␤, and c-Met. In conclusion, in a lethal form of acute viral hepatitis, CT-1 increases animal survival by attenuating inflammation and activating cytoprotective mechanisms, thus representing a promising therapy for ALF of viral origin.Acute liver failure (ALF) arises as a result of extensive hepatocellular damage that exceeds the liver's capacity to regenerate. Depending on the interval between the onset of jaundice and that of encephalopathy, ALF can be categorized into hyperacute (less than 1 week), acute (between 1 and 4 weeks) and subacute (more than 4 weeks). Etiologic factors include viral infections, drugs, biological toxins, metabolic disorders, and ischemia, but it is not unusual for this syndrome to arise without any known causative agent (22).ALF is one of the most challenging human conditions requiring critical care. Therapy is merely supportive and oriented to the correction of complications. Survival is poor and liver transplantation is the only definitive treatment for patients with severe ALF. However, the indication for liver transplantation relies on prognostic assessment, and this lacks accuracy. In transplanted patients mortality is about 10%, but ca. 30% of patients with ALF die without having access to transplantation (24). Thus, novel medical treatments for this condition are urgently needed. With the exception of N-acetylcysteine, which can prevent glutathione depletion...

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Section: Discussionmentioning

confidence: 99%

Cardiotrophin-1 Promotes a High Survival Rate in Rabbits with Lethal Fulminant Hepatitis of Viral Origin

Tuñón

Miguel

Crespo

et al. 2011

J Virol

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“…Urinary F2-isoprostanes (IPF2) were determined by ELISA using 8-epi-PGF 2α as the standard (Cayman Laboratories, Ann Arbor, Mich., USA). Serum and urinary cardiotrophin-1 (CT-1) were analyzed using an ELISA assay developed at the Center for Applied Medical Research; a monoclonal anti-mouse CT-1 antibody was used as capture antibody and a biotinylated anti-rat CT-1 polyclonal antibody (MAB 438) was used as a detection antibody (R&D) [20], at a dilution of 1/20 for plasma and 1/10 for urine.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Intravenous and Oral Hydration in the Prevention of Contrast-Induced Acute Kidney Injury in Low-Risk Patients: A Randomized Trial

Martín-Moreno

Varo²,

Martı́nez-Ansó

et al. 2015

Nephron

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Aims: Contrast-induced acute kidney injury (CI-AKI) is a common cause of renal failure. We evaluated the effectiveness of oral sodium citrate versus intravenous (IV) sodium bicarbonate for CI-AKI prophylaxis as well as their influence on kidney injury biomarkers. Material and Methods: A randomized, controlled, single-center study including 130 hospitalized patients (62.3% men), who were randomized to receive sodium bicarbonate (1/6 men, 3 ml/kg/h for 1 h; n = 43), oral sodium citrate (75 ml/10 kg divided into 4 doses; n = 43) or nonspecific hydration (n = 44) before contrast administration, was conducted. Serum creatinine and kidney injury biomarkers (cystatin C, neutrophil gelatinase-associated lipocalin, interleukin-8, F2-isoprostanes and cardiotrophin-1 [CT-1]) were assessed. Results: Incidence of CI-AKI was 9.2% with no differences found between hydration groups: 7.0% in sodium bicarbonate group, 11.6% in oral sodium citrate group and 9.1% in the nonspecific hydration group. Urinary creatinine and urinary CT-1/creatinine ratio decreased 4 h after contrast infusion (p < 0.001), but none of the biomarkers assessed were affected by the treatments. Conclusions: There were no differences in hydration with oral sodium citrate and IV sodium bicarbonate for the prophylaxis of CI-AKI. Therefore, oral hydration represents a safe, inexpensive and practical method for preventing CI-AKI in low-risk patients. No effect on biomarkers for kidney injury could be demonstrated.

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“…Transplantation of EPCs offers the potential for targeted treatment of ischemic diseases such as myocardial [55], hind-limb ischemia [56], and renal injury [57]. Considerable efforts have been made to monitor the fate of endothelial progenitor cells fate in vivo using the in vivo molecular imaging modalities, such as PET [58], computed tomography(CT) [59], MRI [56], BLI [60]. Micro-CT has been applied in studies of EPCs in rat, pig and human beings.…”

Section: Imaging Of Endothelial Progenitor Cell Therapymentioning

confidence: 99%

Current Perspectives on Molecular Imaging for Tracking Stem Cell Therapy

Tong¹,

Zhao²,

He³

et al. 2013

Medical Imaging in Clinical Practice

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Treatment of murine fulminant hepatitis with genetically engineered endothelial progenitor cells

Cited by 14 publications

References 22 publications

Cardiotrophin-1 Promotes a High Survival Rate in Rabbits with Lethal Fulminant Hepatitis of Viral Origin

Cardiotrophin-1 Promotes a High Survival Rate in Rabbits with Lethal Fulminant Hepatitis of Viral Origin

Comparison of Intravenous and Oral Hydration in the Prevention of Contrast-Induced Acute Kidney Injury in Low-Risk Patients: A Randomized Trial

Current Perspectives on Molecular Imaging for Tracking Stem Cell Therapy

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