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Caveolin-1-dependent tenascin C inclusion in extracellular vesicles is required to promote breast cancer cell malignancy
(2023)
America Campos
;
Renato Burgos-Ravanal
;
Lorena Lobos-González
;
Ricardo Huilcamán
;
María Fernanda González
<jats:p> Background: Elevated expression of CAV1 in breast cancer increases tumor progression. Extracellular vesicles (EVs) from CAV1-expressing MDA-MB-231 breast cancer cells contain Tenascin C (TNC), but the relevance of TNC remained to be defined. Methods: EVs were characterized by nanotracking analysis, microscopy and western blotting. The uptake of EVs by cells was studied using flow cytometry. The effects of EVs on breast cancer cells were tested in migration, invasion, colony formation and in vivo assays. Results: EVs were taken up by cells; however, only those containing TNC promoted invasiveness. In vivo, EVs lacking TNC ceased to promote tumor growth. Conclusion: CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer. </jats:p>
Scopus© Citations 7 1
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Small molecules to perform big roles: The search for Parkinson's and Huntington's disease therapeutics
(2023)
Rodrigo Pérez-Arancibia
;
Marisol Cisternas-Olmedo
;
Denisse Sepúlveda
;
Paulina Troncoso-Escudero
;
Rene L. Vidal
<jats:p>Neurological motor disorders (NMDs) such as Parkinson's disease and Huntington's disease are characterized by the accumulation and aggregation of misfolded proteins that trigger cell death of specific neuronal populations in the central nervous system. Differential neuronal loss initiates the impaired motor control and cognitive function in the affected patients. Although major advances have been carried out to understand the molecular basis of these diseases, to date there are no treatments that can prevent, cure, or significantly delay the progression of the disease. In this context, strategies such as gene editing, cellular therapy, among others, have gained attention as they effectively reduce the load of toxic protein aggregates in different models of neurodegeneration. Nevertheless, these strategies are expensive and difficult to deliver into the patients' nervous system. Thus, small molecules and natural products that reduce protein aggregation levels are highly sought after. Numerous drug discovery efforts have analyzed large libraries of synthetic compounds for the treatment of different NMDs, with a few candidates reaching clinical trials. Moreover, the recognition of new druggable targets for NMDs has allowed the discovery of new small molecules that have demonstrated their efficacy in pre-clinical studies. It is also important to recognize the contribution of natural products to the discovery of new candidates that can prevent or cure NMDs. Additionally, the repurposing of drugs for the treatment of NMDs has gained huge attention as they have already been through clinical trials confirming their safety in humans, which can accelerate the development of new treatment. In this review, we will focus on the new advances in the discovery of small molecules for the treatment of Parkinson's and Huntington's disease. We will begin by discussing the available pharmacological treatments to modulate the progression of neurodegeneration and to alleviate the motor symptoms in these diseases. Then, we will analyze those small molecules that have reached or are currently under clinical trials, including natural products and repurposed drugs.</jats:p>
3Scopus© Citations 21
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New Perspectives to Improve Mesenchymal Stem Cell Therapies for Drug-Induced Liver Injury
(2022)
EZQUER, EDUARDO FERNANDO
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HUANG, YA LIN
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EZQUER, EDUARDO MARCELO
<jats:p>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.</jats:p>
Scopus© Citations 10 1
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Microencapsulation of cellular aggregates composed of differentiated insulin and glucagon-producing cells from human mesenchymal stem cells derived from adipose tissue
(2020)
Claudia Jara
;
Felipe Oyarzun-Ampuero
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Flavio Carrión
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Esteban González-Echeverría
;
Claudio Cappelli
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>In type I diabetes mellitus (T1DM) pancreatic β cells are destroyed. Treatment entails exogenous insulin administration and strict diet control, yet optimal glycemic control is hardly attainable. Islet transplant could be an alternative in patients with poor glycemic control, but inefficient islet purification and autoimmune response of patients is still a challenge. For these reasons, it is necessary to explore new cellular sources and immunological isolation methods oriented to develop T1DM cell-based therapies.</jats:p> </jats:sec><jats:sec> <jats:title>Aims</jats:title> <jats:p>We postulate human adipose-derived stem cell (hASC) as an adequate source to generate pancreatic islet cells in vitro, and to produce islet-like structures. Furthermore, we propose microencapsulation of these aggregates as an immunological isolation strategy.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>hASC obtained from lipoaspirated fat tissue from human donors were differentiated in vitro to insulin (Ins) and glucagon (Gcg) producing cells. Then, insulin producing cells (IPC) and glucagon producing cells (GPC) were cocultured in low adhesion conditions to form cellular aggregates, and later encapsulated in a sodium alginate polymer. Expression of pancreatic lineage markers and secretion of insulin or glucagon in vitro were analyzed.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>The results show that multipotent hASC efficiently differentiate to IPC and GPC, and express pancreatic markers, including insulin or glucagon hormones which they secrete upon stimulation (fivefold for insulin in IPC, and fourfold for glucagon, compared to undifferentiated cells). In turn, calculation of the Feret diameter and area of cellular aggregates revealed mean diameters of ~ 80 µm, and 65% of the aggregates reached 4000 µm<jats:sup>2</jats:sup> at 72 h of formation. IPC/GPC aggregates were then microencapsulated in sodium-alginate polymer microgels, which were found to be more stable when stabilized with Ba<jats:sup>2+</jats:sup>, yielding average diameters of ~ 300 µm. Interestingly, Ba<jats:sup>2+</jats:sup>-microencapsulated aggregates respond to high external glucose with insulin secretion.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The IPC/GPC differentiation process from hASC, followed by the generation of cellular aggregates that are later microencapsulated, could represent a possible treatment for T1DM.</jats:p> </jats:sec>
16Scopus© Citations 9
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Potential Novel Strategies for the Treatment of Dental Pulp-Derived Pain: Pharmacological Approaches and Beyond
(2019)
SCHUH, CHRISTINA
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Bruna Benso
;
Sebastian Aguayo
12 1Scopus© Citations 21
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Exosomes on the border of species and kingdom intercommunication
(2019)
SCHUH, CHRISTINA
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Jimena Cuenca
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Francisca Alcayaga-Miranda
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Maroun Khoury
1Scopus© Citations 48 4
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Preclinical evaluation of cell-based strategies to prevent or treat bronchopulmonary dysplasia in animal models: a systematic review
(2018)
Flore Lesage
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JIMENEZ GREZ, JULIO ALBERTO
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Jaan Toelen
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Jan Deprest
Scopus© Citations 12 1
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Two complementary strategies to improve cell engraftment in mesenchymal stem cell-based therapy: Increasing transplanted cell resistance and increasing tissue receptivity
(2016)
EZQUER, EDUARDO FERNANDO
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EZQUER, EDUARDO MARCELO
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Jose M. Vicencio
;
Sebastián D. Calligaris
9Scopus© Citations 46
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The Reparative Abilities of Menstrual Stem Cells Modulate the Wound Matrix Signals and Improve Cutaneous Regeneration
(2018)
Jimena Cuenca
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Alice Le-Gatt
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Valentina Castillo
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Jose Belletti
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Macarena Díaz
18Scopus© Citations 47
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Gene and cell therapy on the acquisition and relapse-like binge drinking in a model of alcoholism: translational options
(2019)
Yedy Israel
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Quintanilla, María Elena
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Paola Ezquer
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Mario Morales
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Eduardo Rivera-Meza
26Scopus© Citations 4

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