Naïve or Engineered Extracellular Vesicles from Different Cell Sources: Therapeutic Tools for Kidney Diseases

Abstract

Renal pathophysiology is a multifactorial process involving different kidney structures. Acute kidney injury (AKI) is a clinical condition characterized by tubular necrosis and glomerular hyperfiltration. The maladaptive repair after AKI predisposes to the onset of chronic kidney diseases (CKD). CKD is a progressive and irreversible loss of kidney function, characterized by fibrosis that could lead to end stage renal disease. In this review we provide a comprehensive overview of the most recent scientific publications analyzing the therapeutic potential of Extracellular Vesicles (EV)-based treatments in different animal models of AKI and CKD. EVs from multiple sources act as paracrine effectors involved in cell-cell communication with pro-generative and low immunogenic properties. They represent innovative and promising natural drug delivery vehicles used to treat experimental acute and chronic kidney diseases. Differently from synthetic systems, EVs can cross biological barriers and deliver biomolecules to the recipient cells inducing a physiological response. Moreover, new methods for improving the EVs as carriers have been introduced, such as the engineering of the cargo, the modification of the proteins on the external membrane, or the pre-conditioning of the cell of origin. The new nano-medicine approaches based on bioengineered EVs are an attempt to enhance their drug delivery capacity for potential clinical applications.

A quantitative review of nanotechnology‐based therapeutics for kidney diseases

“…Extracellular vesicles (EVs), lipid bilayer-enclosed nanovesicles ranging from 30 to 1000 nm, are released by a variety of cells (Tang et al, 2022). These EVs have been used as nanocarriers for therapeutic purposes due to their unique membrane composition of various lipid molecules, providing favorable stability in plasma (Ceccotti et al, 2023;Levy et al, 2024;Millard et al, 2018). EVs encapsulate a range of endogenous molecules such as mRNAs, microRNAs, cytokines, and mitochondria from donor cells, enabling intercellular communication in both healthy and diseased states (C. Guo et al, 2023;Herrmann et al, 2021;Mao et al, 2022).…”

“…Furthermore, EVs can be engineered post-isolation to carry exogenous chemicals and biomolecules (Tang et al, 2022). Across the EV landscape, those derived from mesenchymal stem cells (MSCs) have been manipulated to encapsulate therapeutic microRNAs, mRNAs, and proteins and are prominently used in the treatment of renal diseases such as AKI, diabetic kidney disease, and renal fibrosis (Ceccotti et al, 2023;Kosanovic et al, 2023;Tang et al, 2022).…”

State of the Art and New Trends from the Second International StemNet Meeting

“…In the same path, the last presentation of this session was given by Dr. Stefania Bruno (University of Torino, Italy) on the role of purified EVs derived from human liver stem cells (HLSC-EVs) in chronic kidney disease (CKD) and cardiac dysfunction in the remnant kidney murine model [8]. The study provides a foundation for both HLSC contribution to tissue regeneration in liver and kidney injuries and the retained therapeutic properties of HLSC-EVs.…”

Engineered Extracellular Vesicles in Chronic Kidney Diseases: A Comprehensive Review

“…Fourth, these modifications can also reduce the risk of an immune response, rendering engineered EVs safer for long-term CKD treatment. 10 Lastly, engineered EVs can be produced at a larger scale than natural EVs, making them more feasible for clinical applications in CKD therapy. 11 These combined advantages position engineered EVs as a promising avenue for the development of targeted and effective CKD treatments, with the potential to enhance patient outcomes and reduce the burden of this chronic condition.…”