New evidence on the therapeutic potential of extracellular vesicles in kidney injury

Researchers from the Germans Trias i Pujol Research Institute (IGTP) have published a scientific review analysing the therapeutic potential of extracellular vesicles derived from mesenchymal stem cells to address kidney injury. The article, published in the journal Extracellular Vesicles and Circulating Nucleic Acids and featured on the cover, reviews current evidence on how these vesicles can interact with renal tubular epithelial cells.

Kidney disease is a major global health challenge. It includes acute kidney injury, which affects approximately half of patients admitted to intensive care units, and chronic kidney disease -the progression of recurrent or unresolved injury-, which is expected to become the fifth leading cause of death worldwide by 2040.

The Experimental Nephrology and Cell-based Therapies (ENACT) research group at IGTP studies these conditions in the laboratory to improve both their monitoring and treatment. One of its main research lines focuses on exploring the therapeutic use of extracellular vesicles, small structures secreted by cells that can transport molecules with regulatory functions. In this case, the group focuses on vesicles derived from mesenchymal stem cells (MSC-EVs).

How can vesicles help in kidney injury?

The team has recently published a review analysing how MSC-EVs can interact with renal tubular epithelial cells, which are the main cells affected in many forms of kidney injury. When these cells do not repair correctly, they may initiate processes that promote inflammation and fibrosis, contributing to the progression towards chronic kidney disease.

In this context, MSC-EVs have attracted considerable interest because they can carry microRNAs, proteins, or lipids capable of modulating key processes involved in kidney injury, such as apoptosis, inflammation, or oxidative stress. In various experimental models, these vesicles have shown protective effects on damaged tubular cells, reinforcing the idea that they could become a promising therapeutic tool.

A path full of scientific challenges

In addition to reviewing studies on the role of MSC-EVs in kidney injury, the article from ENACT also examines a critical aspect for clinical translation: their ability to reach tubular tissue after intravenous administration. Available data indicate that only a small fraction of injected vesicles reaches the kidney, as a large proportion becomes trapped in organs such as the liver, lungs, or spleen. When they do reach the kidney, however, they can be taken up by tubular cells through specific binding mechanisms that facilitate their entry and the onset of their regulatory effects on target cells.

Other limitations that require further investigation to advance towards clinical application include the high variability between vesicle preparations, differences in isolation or quantification methods, and the lack of standards for comparing doses or procedures. The authors highlight several future research lines that may help overcome these challenges, such as engineering vesicles to improve their targeting to tubular cells, or developing potency assays that can reliably predict their therapeutic effect.

Perspectives from the research team

Linrong Pan, first author of the study and PhD student in the ENACT group at IGTP, explains: "This review aims to narrow the gap between the potential observed in preclinical studies and clinical translation of MSC-EVs for damage to tubular epithelial cells. Through this systematic analysis, we hope to guide future research towards more standardised approaches, based on a better understanding of the biological mechanisms involved and with greater clinical relevance". She adds: "This work will help deepen our understanding of the biodistribution and targeting of extracellular vesicles, and contribute to the development of more precise and effective vesicle-based therapies for the treatment of kidney injury".

In parallel, Marcel·la Franquesa, principal investigator of the study and leader of the ENACT group, notes that "the therapeutic potential of MSC-EVs in kidney diseases is rapidly growing, but important challenges remain in achieving targeted, standardised and truly translatable results in clinical practice. Our group is working to establish robust assays that allow us to predict the therapeutic efficacy of MSC-EVs and advance towards more precise and reliable vesicle-based therapies".

Reference

Pan L, Garcia SG, Font-Morón M, Sanroque-Muñoz M, Clos-Sansalvador M, Garcia GM, Borràs FE, Franquesa M. Beyond preclinical promise: can mesenchymal stromal cell-derived extracellular vesicles reliably target tubular epithelial cells? Extracell Vesicles Circ Nucl Acids. 2025 Sep 23;6(3):580-593. DOI: 10.20517/evcna.2025.54.

Funding

This study was supported by the Instituto de Salud Carlos III (ISCIII) through the project "PI20/00097" and the RICORS networks RD21/0005/0009 and RD24/0004/0005, all co‐funded by the European Union. Pan L is supported by a CSC-UAB fellowship. Garcia SG is supported by a grant from the Catalan Health department ("Departament de Salut") PERIS‐PIF‐Salut (SLT017/20/000158). de Miguel Garcia G is funded by Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación (MICIU/AEI) (DIN2024-01340). Borràs FE and Franquesa M are researchers from Germans Trias i Pujol Health Science Research Institute, supported by the Health Department of the Catalan Government (Generalitat de Catalunya).