HUANG, YA LIN
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HUANG, YA LIN
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yhuang@udd.cl
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57193124138

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2024 2024 2023 2023 2022 2022 2021 2021 2020 2020 2019 2019 2018 2018 2017 2017 0.0 0.0 0.5 0.5 1.0 1.0 1.5 1.5 2.0 2.0 2.5 2.5 3.0 3.0

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Aloe vera peel-derived nanovesicles display anti-inflammatory properties and prevent myofibroblast differentiation

2024 , RAMIREZ PRADA, ORLANDO JOSUÉ , Florencia Pomareda , OLIVARES, MARIA BELEN , HUANG, YA LIN , Gabriela Zavala , Javiera Carrasco-Rojas , Simón Alvarez , Camila Leiva-Sabadini , Valeria Hidalgo , Pablo Romo , SANCHEZ JIMÉNEZ, MATÍAS IGNACIO , Ayleen Vargas , Sebastian Aguayo , SCHUH, CHRISTINA , MARTINEZ ARENAS, JESSICA ISABEL

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Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions

2023 , DE GREGORIO CONCHA, CRISTIAN ALEJANDRO , Evelyng Catalán , Gabriel Garrido , Pilar Morandé , CASTILLO BENNETT, JIMENA VICTORIA , Catalina Muñoz , Glenda Cofré , HUANG, YA LIN , Bárbara Cuadra , Paola Murgas , Margarita Calvo , Fernando Altermatt , Andrew P. South , YUBERO GONCALVEZ, MARIA JOAO , PALISSON ETCHARREN, FRANCIS , EZQUER, EDUARDO MARCELO , FUENTES BUSTOS, MARIA IGNACIA

Abstract Background Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients. Results In order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-β1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1β and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies. Conclusions Our results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients’ chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.

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The Immunoregulatory and Regenerative Potential of Activated Human Stem Cell Secretome Mitigates Acute-on-Chronic Liver Failure in a Rat Model

2024 , Barbara Cuadra , Veronica Silva , HUANG, YA LIN , Yael Diaz , Claudio Rivas , Cristobal Molina , Valeska Simon , Maria Rosa Bono , Bernardo Morales , Mario Rosemblatt , Sebastian Silva , ACUÑA ASTUDILLO, RODRIGO ANTONIO , EZQUER, EDUARDO FERNANDO , EZQUER, EDUARDO MARCELO

Acute-on-chronic liver failure (ACLF) is a syndrome marked by sudden liver function decline and multiorgan failure, predominantly acute kidney injury (AKY), in patients with chronic liver disease. Unregulated inflammation is a hallmark of ACLF; however, the key drivers of ACLF are not fully understood. This study explores the therapeutic properties of human mesenchymal stem cell (MSC) secretome, particularly focusing on its enhanced anti-inflammatory and pro-regenerative properties after the in vitro preconditioning of the cells. We evaluated the efficacy of the systemic administration of MSC secretome in preventing liver failure and AKI in a rat ACLF model where chronic liver disease was induced using by the administration of porcine serum, followed by D-galN/LPS administration to induce acute failure. After ACLF induction, animals were treated with saline (ACLF group) or MSC-derived secretome (ACLF-secretome group). The study revealed that MSC-secretome administration strongly reduced liver histological damage in the ACLF group, which was correlated with higher hepatocyte proliferation, increased hepatic and systemic anti-inflammatory molecule levels, and reduced neutrophil and macrophage infiltration. Additionally, renal examination revealed that MSC-secretome treatment mitigated tubular injuries, reduced apoptosis, and downregulated injury markers. These improvements were linked to increased survival rates in the ACLF-secretome group, endorsing MSC secretomes as a promising therapy for multiorgan failure in ACLF.

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Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy

2017 , EZQUER, EDUARDO FERNANDO , Javiera Bahamonde , Ya-Lin Huang , EZQUER, EDUARDO MARCELO

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IMMUNOMODULATORY AND REGENERATIVE PROPERTIES OF HUMAN MENSENCHYMAL STEM CELLS SECRETOME, PREVENT HEPATIC AND RENAL MULTIPLE ORGAN DYSFUNCTION IN A RAT MODEL OF ACUTE ON CHRONIC LIVER FAILURE

2023 , EZQUER, EDUARDO FERNANDO , EZQUER, EDUARDO MARCELO , CUADRA, BÁRBARA , HUANG, YA LIN , Verónica Silva , VÁSQUEZ, L.

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New Perspectives to Improve Mesenchymal Stem Cell Therapies for Drug-Induced Liver Injury

2022 , EZQUER, EDUARDO FERNANDO , HUANG, YA LIN , EZQUER, EDUARDO MARCELO

Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. Many factors may contribute to the susceptibility of patients to this condition, making DILI a global medical problem that has an impact on public health and the pharmaceutical industry. The use of mesenchymal stem cells (MSCs) has been at the forefront of regenerative medicine therapies for many years, including MSCs for the treatment of liver diseases. However, there is currently a huge gap between these experimental approaches and their application in clinical practice. In this concise review, we focus on the pathophysiology of DILI and highlight new experimental approaches conceived to improve cell-based therapy by the in vitro preconditioning of MSCs and/or the use of cell-free products as treatment for this liver condition. Finally, we discuss the advantages of new approaches, but also the current challenges that must be addressed in order to develop safer and more effective procedures that will allow cell-based therapies to reach clinical practice, enhancing the quality of life and prolonging the survival time of patients with DILI.

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Administration of Secretome Derived from Human Mesenchymal Stem Cells Induces Hepatoprotective Effects in Models of Idiosyncratic Drug-Induced Liver Injury Caused by Amiodarone or Tamoxifen

2023 , HUANG, YA LIN , Silva Villalobos, Verónica , DE GREGORIO CONCHA, CRISTIAN ALEJANDRO , Álvaro A. Elorza , Patricio Léniz , Víctor Aliaga-Tobar , Vinicius Maracaja-Coutinho , Mauricio Budini , EZQUER, EDUARDO MARCELO , EZQUER, EDUARDO FERNANDO

Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. While many factors may contribute to the susceptibility to DILI, obese patients with hepatic steatosis are particularly prone to suffer DILI. The secretome derived from mesenchymal stem cell has been shown to have hepatoprotective effects in diverse in vitro and in vivo models. In this study, we evaluate whether MSC secretome could improve DILI mediated by amiodarone (AMI) or tamoxifen (TMX). Hepatic HepG2 and HepaRG cells were incubated with AMI or TMX, alone or with the secretome of MSCs obtained from human adipose tissue. These studies demonstrate that coincubation of AMI or TMX with MSC secretome increases cell viability, prevents the activation of apoptosis pathways, and stimulates the expression of priming phase genes, leading to higher proliferation rates. As proof of concept, in a C57BL/6 mouse model of hepatic steatosis and chronic exposure to AMI, the MSC secretome was administered endovenously. In this study, liver injury was significantly attenuated, with a decrease in cell infiltration and stimulation of the regenerative response. The present results indicate that MSC secretome administration has the potential to be an adjunctive cell-free therapy to prevent liver failure derived from DILI caused by TMX or AMI.

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