A5032391597- Mesenchymal stem cell research
- Liver physiology and pathology
- Cancer Cells and Metastasis
- Fibroblast Growth Factor Research
- Pancreatic function and diabetes
- Immunotherapy and Immune Responses
- Liver Disease Diagnosis and Treatment
- Bone and Dental Protein Studies
- Proteoglycans and glycosaminoglycans research
- Cancer, Hypoxia, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Virus-based gene therapy research
- Cancer Research and Treatments
- CAR-T cell therapy research
- MicroRNA in disease regulation
- Tissue Engineering and Regenerative Medicine
- Immune Cell Function and Interaction
- Extracellular vesicles in disease
- Diabetes and associated disorders
- RNA Interference and Gene Delivery
- Digestive system and related health
- Phagocytosis and Immune Regulation
- TGF-β signaling in diseases
- Cancer, Lipids, and Metabolism
- Folate and B Vitamins Research
Austral University
2015-2024
Consejo Nacional de Investigaciones Científicas y Técnicas
2016-2024
Fundación Ciencias Exactas y Naturales
2020
University of Buenos Aires
2020
Instituto de Investigaciones en Ciencias de la Salud
2020
Gene Therapy Laboratory
2012-2020
Institute for Medical Research
2016
Indiana University School of Medicine
2012
Stony Brook University
2007
Liver cirrhosis involves chronic wound healing and fibrotic processes. Mesenchymal stromal cells (MSCs) are multipotent adult progenitor that used as vehicles of therapeutic genes. Insulin growth factor like-I (IGF-I) was shown to counteract liver fibrosis. We aimed at analyzing the effect applying IGF-I overexpressing mouse bone marrow-derived MSCs on hepatic Fibrosis induced by thioacetamide application or bile duct ligation. engineered produce green fluorescent protein (GFP) (AdGFP-MSCs)...
Hepatocellular carcinoma (HCC) is the fifth most common cancer and third cause of cancer-related death. Fibrogenesis an active process characterized by production several proinflammatory cytokines, chemokines growth factors. It involves activation hepatic stellate cells (HSCs) which accumulate at site injury are main source extracellular matrix deposits. There no curative treatments for advanced HCC, thus, new therapies urgently needed. Mesenchymal stromal (MSCs) have ability to migrate...
The tumor microenvironment (TME) represents a complex interplay between different cellular components, including cells and cancer stem (CSCs), with the associated stroma; such interaction promotes immune escape sustains growth. Several experimental approaches for therapy are focused on TME remodeling, resulting in increased antitumor effects. We previously demonstrated that hyaluronan synthesis inhibitor 4-methylumbelliferone (4Mu) decreases liver fibrosis induces activity hepatocellular...
Cirrhosis is characterized by an excessive accumulation of extracellular matrix components including hyaluronic acid (HA) and widely considered a preneoplastic condition for hepatocellular carcinoma (HCC).4-Methylumbelliferone (4MU) inhibitor HA synthesis has anticancer activity in orthotopic HCC model with underlying fibrosis.Our aim was to explore the effects inhibition 4MU orally administered on tumor microenvironment.Hepa129 cells were inoculated orthotopically C3H/HeJ male mice fibrosis...
Several reports described the migration of human mesenchymal stromal cells (MSCs) towards tumor-released factors. Autocrine motility factor (AMF) is produced by several tumors including hepatocellular carcinoma (HCC). The aim this study was to analyze AMF involvement on MSC HCC.Production HCC evaluated western analysis. effects MSCs from different sources (bone marrow, adipose tissue and perivascular umbilical cord) were analyzed using in vitro assay; metalloproteinase 2 (MMP2) activity...
Introduction Secreted Protein, Acidic and Rich in Cysteine (SPARC) is a matricellular protein involved many biological processes found over-expressed cirrhotic livers. By mean of genetic approach we herein provide evidence from different vivo liver disease models suggesting profibrogenic role for SPARC. Methods Two fibrosis, based on TAA administration bile duct ligation, were developed SPARC wild-type (SPARC+/+) knock-out (SPARC−/−) mice. Hepatic expression was analyzed by qPCR. Fibrosis...
// Juan Bayo 1 , Alejandrina Real Esteban J. Fiore Mariana Malvicini Leonardo Sganga 6 Marcela Bolontrade 2 Oscar Andriani 3 Carolina Bizama 4 Cristóbal Fresno 5 Osvaldo Podhajcer Elmer Fernandez Manuel Gidekel 7, 8 Guillermo D. Mazzolini 1, 3, * G. García Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad Ciencias Biomédicas, CONICET, Universidad Austral, Buenos Aires, Argentina Stem Cells IBYME, Liver Unit, Hospital Universitario Derqui-Pilar,...
Abstract Obesity, metabolic syndrome, and type 2 diabetes, three strongly interrelated diseases, are associated to increased morbidity mortality worldwide. The pathogenesis of obesity-associated disorders is still under study. Secreted protein acidic rich in cysteine (SPARC) a matricellular glycoprotein expressed many cell types including adipocytes, parenchymal, non-parenchymal hepatic cells pancreatic cells. Studies have demonstrated that SPARC inhibits adipogenesis promotes insulin...
Abstract Hyaluronic acid (HA) is a glycosaminoglycan of extracellular matrix related to cell surface which interacts with various types. To understand the role HA during hepatocarcinogenesis, we assessed effect inhibition deposition and its association heterogeneous hepatocellular carcinoma (HCC) cells. In this study, used transgenic mice C57BL/6J-Tg(Alb1HBV)44Bri/J (HBV-TG) normal C57BL/6 J (WT) for in vivo while HCC cells Huh7 JHH6 as vitro models. Both models were treated an inhibitor...
Non-alcoholic fatty liver (NAFLD) and its more serious form non-alcoholic steatohepatitis increase risk of hepatocellular carcinoma (HCC). Lipid metabolic alterations role in HCC development remain unclear. SPARC (Secreted Protein, Acidic Rich Cysteine) is involved lipid metabolism, NAFLD diabetes, but the effects on hepatic metabolism unknown. The aim this study was to evaluate context NAFLD.Primary hepatocyte cultures from knockout (SPARC-/- ) or wild-type (SPARC+/+ mice, HepG2 cells were...
Abstract Background Cirrhosis is a major health problem worldwide and new therapies are needed. Hepatic macrophages (hMø) have pivotal role in liver fibrosis, being able to act both its promotion resolution. It well-known that mesenchymal stromal cells (MSCs) can modulate the immune/inflammatory cells. However, effects of MSCs over hMø context fibrosis remain unclear. We previously described evidence antifibrotic vivo applying MSCs, which were enhanced by forced overexpression insulin-like...
We studied the impact of high prolactin titers on liver and adipocyte gene expression related to glucose insulin homeostasis in correlation with obesity onset. To that end we used mutant female mice selectively lack dopamine type 2 receptors (D2Rs) from pituitary lactotropes (lacDrd2KO), which have chronic levels associated increased body weight, marked increments fat depots, size, serum lipids, a metabolic phenotype intensifies age. LacDrd2KO two developmental ages, 5 10 mo, were used. In...
Objective The RHO family of GTPases, particularly RAC1, has been linked with hepatocarcinogenesis, suggesting that their inhibition might be a rational therapeutic approach. We aimed to identify and target deregulated members in human hepatocellular carcinoma (HCC). Design studied expression deregulation, clinical prognosis transcription programmes relevant HCC using public datasets. potential RAC1 inhibitors was study vitro vivo. RNA-Seq analysis correlation the three different datasets...
Abstract Hepatocellular carcinoma (HCC) arises in the setting of advanced liver fibrosis, a dynamic and complex inflammatory disease. The tumor microenvironment (TME) is mixture cellular components including cancer cells, stem cells (CSCs), tumor-associated macrophages (TAM), dendritic (DCs), which might drive to progression resistance therapies. In this work, we study effects 4-methylumbelliferone (4Mu) on TME how change could be exploited promote potent immune response against HCC. First,...
The use of conventional cytotoxic agents at metronomic schedules, alone or in combination with targeted immunotherapy, is being explored as a promising anticancer strategy. We previously reported potent antitumor effect single low-dose cyclophosphamide and interleukin-12 (IL-12) gene therapy against advanced gastrointestinal carcinoma, mice. Here, we assessed whether the delivery IL-12 by together exerts effects murine model colorectal carcinoma. This was able, least part, to reverse...
We have previously demonstrated that a low dose of cyclophosphamide (Cy) combined with gene therapy interleukin-12 (AdIL-12) has synergistic, although limited, antitumoral effect in mice colorectal carcinoma. The main mechanism involved the efficacy Cy+AdIL-12 was induction specific immune response mediated by cytotoxic T lymphocytes. Our current aims were to evaluate effects 4-methylumbelliferone (4Mu), selective inhibitor hyaluronan (HA) synthesis, on tumor microenvironment (TME) and...
Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies urgently needed use mesenchymal stromal cells (MSCs) as carrier genes emerging a promising option. Different sources MSCs being studied for cell therapy bone marrow-derived most extensively explored; however, birth associated-tissues represent very source. The aim this work was to compare in vitro...
Abstract Background Mesenchymal stromal cells (MSCs) tropism for tumours allows their use as carriers of antitumoural factors and in vitro transcribed mRNA (IVT mRNA) is a promising tool effective transient expression without insertional mutagenesis risk. Granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine with antitumor properties by stimulating the specific immune response. The aim this work was to generate modified MSCs IVT transfection overexpress GM-CSF determine...
We have shown that ex vivo pre-conditioning of bone marrow-derived dendritic cells (DC) with low molecular weight hyaluronan (LMW HA) induces antitumor immunity against colorectal carcinoma (CRC) in mice. In the present study we investigated effects LMW HA priming on human-tumor-pulsed monocytes-derived (DC/TL) obtained from healthy donors and patients CRC. treatment resulted an improved maturation state DC/TL enhanced mixed leucocyte reaction activity vivo. Importantly, increased their...
The Rho GTPase Rac1 is involved in the control of cytoskeleton reorganization and other fundamental cellular functions. Aberrant activity its regulators common human cancer. In particular, deregulated expression/activity Rac GEFs, responsible for activation, has been associated to a metastatic phenotype drug resistance. Thus, development novel Rac1-GEF interaction inhibitors promising strategy finding new preclinical candidates. Here, we studied structure-activity relationships within family...