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Institution

University of the Andes, Chile

EducationSantiago, Chile
About: University of the Andes, Chile is a education organization based out in Santiago, Chile. It is known for research contribution in the topics: Population & Phonation. The organization has 743 authors who have published 750 publications receiving 5710 citations. The organization is also known as: UAndes.


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Journal ArticleDOI
TL;DR: Treatment with 15 mM acetaminophen induced a toxic response in the hepatic construct that was similar to published studies on animal and other in vitro models, thus providing a proof-of-concept demonstration of the utility of this liver-on-a-chip platform for toxicity assessment.
Abstract: The inadequacy of animal models in correctly predicting drug and biothreat agent toxicity in humans has resulted in a pressing need for in vitro models that can recreate the in vivo scenario. One of the most important organs in the assessment of drug toxicity is liver. Here, we report the development of a liver-on-a-chip platform for long-term culture of three-dimensional (3D) human HepG2/C3A spheroids for drug toxicity assessment. The bioreactor design allowed for in situ monitoring of the culture environment by enabling direct access to the hepatic construct during the experiment without compromising the platform operation. The engineered bioreactor could be interfaced with a bioprinter to fabricate 3D hepatic constructs of spheroids encapsulated within photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. The engineered hepatic construct remained functional during the 30 days culture period as assessed by monitoring the secretion rates of albumin, alpha-1 antitrypsin, transferrin, and ceruloplasmin, as well as immunostaining for the hepatocyte markers, cytokeratin 18, MRP2 bile canalicular protein and tight junction protein ZO-1. Treatment with 15 mM acetaminophen induced a toxic response in the hepatic construct that was similar to published studies on animal and other in vitro models, thus providing a proof-of-concept demonstration of the utility of this liver-on-a-chip platform for toxicity assessment.

436 citations

Journal ArticleDOI
TL;DR: In this article, the authors evaluated the safety and efficacy of the infusion of UC-MSC in patients with chronic stable HFrEF under optimal medical treatment and found that the infusion resulted in a 55-fold increase in the expression of Hepatocyte Growth Factor (HGF), known to be involved in cell migration and immunoregulation.
Abstract: Rationale: Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. While bone marrow-derived mesenchymal stem cells (BM-MSCs) have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction (HFrEF), no clinical trial has evaluated UC-MSCs in these patients. Objective: Evaluate the safety and efficacy of the infusion of UC-MSC in patients with chronic stable HFrEF. Methods and Results: HFrEF patients under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile) (1x10 6 cells/Kg) or placebo (n=15 per group). UC-MSCs in vitro , compared to BM-MSCs, displayed a 55-fold increase in the expression of Hepatocyte Growth Factor (HGF), known to be involved in myogenesis, cell migration and immunoregulation. UC-MSC treated patients presented no adverse events related to the cell infusion and none of the patients tested at 0, 15 and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6 and 12 months of follow-up assessed both through transthoracic echocardiography (p=0.0167 versus baseline) and cardiac magnetic resonance imaging (p=0.025 versus baseline). Echocardiographic LVEF change from baseline to month 12 differed significantly between groups (+7.07±6.22% vs +1.85±5.60, p=0.028). In addition, at all follow-up time points, UC-MSCs treated patients displayed improvements of NYHA functional class (p=0.0167 versus baseline) and MLHFQ (p<0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias or incident malignancy. Conclusions: Intravenous infusion of UC-MSC was safe in this group of patients with stable HFrEF under optimal medical treatment. Improvements in left ventricular function, functional status and quality of life were observed in patients treated with UC-MSCs. Trial registration number : NCT01739777. Registry URL: https://clinicaltrials.gov/ct2/show/NCT01739777.

270 citations

Journal ArticleDOI
TL;DR: In this paper, the role of mesenchymal stem cells (MSCs) in the secretion of antimicrobial peptides and proteins (AMPs) has been investigated in pre-clinical models of sepsis, acute respiratory distress syndrome and cystic fibrosis related infections.
Abstract: While mesenchymal stem cells (MSCs)-based therapy appears to be promising, there are concerns regarding possible side effects related to the unwanted suppression of antimicrobial immunity leading to an increased risk of infection. Conversely, recent data show that MSCs exert strong antimicrobial effects through indirect and direct mechanisms, partially mediated by the secretion of antimicrobial peptides and proteins (AMPs). In fact, MSCs have been reported to increase bacterial clearance in pre-clinical models of sepsis, acute respiratory distress syndrome and cystic fibrosis related infections. This article reviews the current evidence regarding the direct antimicrobial effector function of MSCs, focusing mainly on the role of MSCs-derived AMPs. The strategies that might modulate the expression and secretion of these AMPs, leading to enhanced antimicrobial effect are highlighted. Furthermore, studies evaluating the presence of AMPs in the cargo of extracellular vesicles (EVs) are underlined as perspective opportunities to develop new drug delivery tools. The antimicrobial potential of MSCs-derived EVs can also be heightened through cell conditioning and/or drug loading. Finally, improving the pharmacokinetics and delivery, in addition to deciphering the multi-target drug status of AMPs, should synergistically lead to key advances against infections caused by drug resistant strains.

178 citations

Journal ArticleDOI
TL;DR: This article analyzed a dataset of 2390 completed ICOs, which raised a total of $12 billion in capital, nearly all since January 2017, and found evidence of significant ICO underpricing, with average returns of 179% from the ICO price to the first day's opening market price, over a holding period that averages just 16 days.
Abstract: We analyze a dataset of 2390 completed ICOs, which raised a total of $12 billion in capital, nearly all since January 2017. We find evidence of significant ICO underpricing, with average returns of 179% from the ICO price to the first day's opening market price, over a holding period that averages just 16 days. After trading begins, tokens continue to appreciate in price, generating average buy-and-hold abnormal returns of 48% in the first 30 trading days. We also study the determinants of ICO underpricing and relate cryptocurrency prices to Twitter activity.

117 citations

Journal ArticleDOI
TL;DR: The involvement of the innate immune system in the establishment of a physiological environment that favors pregnancy and possible alterations related to the development of PE are discussed.
Abstract: Normal pregnancy is considered as a Th2 type immunological state that favors an immune-tolerance environment in order to prevent fetal rejection. PE has been classically described as a Th1/Th2 imbalance; however, the Th1/Th2 paradigm has proven insufficient to fully explain the functional and molecular changes observed during normal/pathological pregnancies. Recent studies have expanded the Th1/Th2 into a Th1⁄Th2⁄Th17 and regulatory T (Treg) cells paradigm and where dendritic cells could have a crucial role. Recently, some evidence has emerged supporting the idea that mesenchymal stem cells might be part of the feto-maternal tolerance environment. This review will discuss the involvement of the innate immune system in the establishment of a physiological environment that favors pregnancy and possible alterations related to the development of preeclampsia.

112 citations


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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20243
20236
202222
202188
202072
201959