A Researcher Live Series: November - December 2022

Emerging Biomedical Opportunities for Extracellular Vesicles


During the last decade, extracellular vesicles (EVs) have emerged as a strong and attractive field of research. EVs are bi-layered nano-sized vesicles produced by most cell types with the capacity to package and deliver molecules such as RNAs and proteins to other cells, playing an important role in intercellular communication. Although sharing some structural molecular components, the composition of EVs mostly depends on the secreting cell type and their physiological status. Hence, their potential as reservoirs of biomarkers has been explored mainly due to their particular composition and presence in the extracellular milieu and biofluids. Moreover, EVs have also been envisaged as drug and gene delivery carriers for cell-free therapeutic approaches because of their maintenance of homeostasis and protected environment. 

In this series, we invite experts to discuss their work in EV biology and potential biomedical research opportunities. 

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Programme

Topic

Date

Time

Studying tetraspanins in extracellular vesicles

with Dr María Yañez-Mo, Autonomous University of Madrid

Monday, 28 Nov

3 pm GMT

Assessment of exRNAs for monitoring CNS related injury and disease

with Dr Kendall Van Keuren Jensen, Translational Genomics Research Institute, Phoenix

Wednesday, 30 Nov

5.30 pm GMT

Therapeutic potential of extracellular vesicles

with Dr Marta Moguió-Tortajada, Germans Trias i Pujol Research Institute

Thursday, 1 Dec

3 pm GMT

Pharmacokinetics and biodistribution of extracellular vesicles after intravenous and intranasal administration in macaques

with Dr Tom Driedonks, University Medical Center Utrecht

Thursday, 5 Dec

2 pm GMT

 

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Studying tetraspanins in extracellular vesicles

with Dr María Yañez-Mo, Autonomous University of Madrid

maria-yanez-mo-1

Tetraspanins are a family of four transmembrane proteins that ensemble microdomains at the plasma membrane and membranes in the endosomal compartments. Our and others´ data suggest that they play an important role in EV cargo selection and have been widely used as EV markers. We have, on the one hand, used our tetraspanin-based tools for the development of different EV-related techniques, and on the other, studied their role in EV formation. These studies led us to describe a new role for tetraspanins as regulators of non-canonical mitophagy and, therefore, cell metabolic fitness.

About the speaker

Dr Maria Yáñez earned her PhD in Biochemistry and Molecular Biology from the Universidad Autónoma of Madrid (UAM). As a postdoctoral researcher, she was in charge of setting up the first confocal facility able to perform time-lapse microscopy in living cells in Spain. Since 2014, she is an associate professor in the department of molecular biology at UAM. Her main research interest focuses on the biology and functionality of tetraspanins, important proteins involved in intracellular connections and in extracellular vesicles, and exosome’s biogenesis. Her scientific production accounts for more than 50 publications, and she is one of the most cited Spanish female scientists, as recently reported by the Spanish National Research Council. In 2011, she was a founding member of the International Society for Extracellular vesicles (ISEV) and, a year later, she was part of the founding committee of the Spanish Group of Research in Extracellular vesicles (GEIVEX).


Assessment of exRNAs for monitoring CNS related injury and disease

with Dr Kendall Van Keuren Jensen, Translational Genomics Research Institute, Phoenix

Kendall Van Keuren Jensen H

We have looked at the transcriptomic profile of several different biofluids for their tissue-enriched contents. One area of research that we are particularly focused on is monitoring the exRNAs potentially associated with CNS tissues. A characterization of the types of exRNAs in different biofluids will be presented. We will discuss both small and long RNA transcriptomes. Improvements on how to get brain-derived information will also be presented.

About the speaker

Dr Van Keuren-Jensen received her PhD from Stonybrook University in New York, at Cold Spring Harbor Laboratory. After a short postdoctoral fellowship at Harvard University, she joined TGen, the Translational Genomics Research Institute in Phoenix. Currently, she is a TGen Deputy Director, Professor in the Neurogenomics Division, and Director of the Center for Non-Invasive Diagnostics. Her lab is interested in understanding injury and disease in the central nervous system (CNS). Due to the difficulty of accessing this very protected area, her research efforts focus on the study of extracellular RNAs (exRNAs) in peripheral circulation as promising tools for monitoring the CNS, providing information about cellular changes occurring in different tissues. In this sense, extracellular vesicles and exosomes confer a protected environment for biomolecules, which makes them an attractive and promising source of disease biomarkers.


Therapeutic potential of extracellular vesicles

with Dr Marta Moguió-Tortajada, Germans Trias i Pujol Research Institute

Marta-Monguio-Tortajada

Extracellular vesicles (EV) are becoming increasingly studied, not only to better understand cell communication but to be exploited as a new cell-free therapeutic approach.

Specifically, EV secreted by mesenchymal stromal cells can modulate inflammation and promote tissue healing, features that can be used to treat tissue injury such as myocardial infarction.

In this chapter, Dr Marta Monguió-Tortajada will summarize knowledge of EV therapeutic properties and strategies to foster their clinical use.

About the speaker

Dr Marta Monguió-Tortajada is a postdoctoral researcher working on extracellular vesicles (EV) and immunology in the context of cardiac inflammation and repair at the ICREC group led by Dr Bayes-Genis in the Germans Trias i Pujol Research Institute (IGTP) in Badalona, Spain. She graduated in Biotechnology in 2012 (UAB) during which time she was granted a scholarship to attend the University of Technology of Sydney (2010). She did her MSc in Advanced Immunology (UB-UAB) at the group of Dr Borràs (IGTP), where she also continued with her PhD. She was granted the FI-DGR fellowship (AGAUR, Generalitat de Catalunya) to pursue her research in Immunology. Her work focused on the cellular and EV-based mechanisms of MSC for immunomodulation and tissue repair in the context of myocardial infarction, which she completed summa cum laude (2018). Dr Monguió-Tortajada is an active member of ISEV (International Society of Extracellular Vesicles) and co-chairs the Taskforce for clinical translation of EV. She was a founding member of the Women in Science working group of the Can Ruti Campus (IGTP).


Pharmacokinetics and biodistribution of extracellular vesicles after intravenous and intranasal administration in macaques

with Dr Tom Driedonks, University Medical Center Utrecht

Tom Driedonks-1

On this occasion, Dr Driedonks will present to us his very last work related to the potential role of EVs as therapeutic carriers. What would happen when injecting EVs into a mammal's body? Let’s hear it from the expert! 

Extracellular vesicles (EVs) have potential in disease treatment since they can be loaded with therapeutic molecules and engineered for retention by specific tissues. However, questions remain on optimal dosing, administration, and pharmacokinetics. Previous studies have addressed biodistribution and pharmacokinetics in rodents, but little evidence is available for larger animals. 

Here, we investigated the pharmacokinetics and biodistribution of Expi293F-derived EVs labelled with a highly sensitive nanoluciferase reporter (palmGRET) in a non-human primate model (Macaca nemestrina), comparing intravenous (IV) and intranasal (IN) administration over a 125-fold dose range. Our findings from this baseline study in macaques will help to inform future research and therapeutic development of EVs.

About the speaker

Dr Driedonks graduated in Biotechnology in 2011 (Wageningen University) and obtained his PhD in 2019 from Utrecht University while working in the lab of Dr Esther Nolte-’t Hoen. During his PhD, his work focused on unrevealing the RNA content of extracellular vesicles and their role in intercellular communication in inflammatory conditions. After a postdoctoral stage, in 2020, at Johns Hopkins Institute (Baltimore, USA), he came back to the Netherlands (Universitair Medisch Centrum Utrecht), where he is currently working as a postdoctoral researcher. His last work, available as a preprint in biorxiv.org, investigated different administration routes and targeting of EVs as potential therapeutic tools. Moreover, Dr Driedonks is part of the communication office of the Student Network on EVs (SNEV) and became a Member-at-Large of ISEV in 2022.