Kidney Week 2025 Annual Meeting-Extracellular Vesicle-Based Therapeutics for CKD: The Way of the Future

Video Transcription

Video Summary

This symposium session introduced extracellular vesicles (EVs) and their emerging therapeutic potential in kidney disease. Dr. Monika Huhn outlined EV diversity (ectosomes, exosomes, apoptotic bodies and other large subtypes) and emphasized heterogeneity: EV fractions separated by size can differ in protein markers, uptake by specific cell types, and functional effects. EV uptake commonly occurs via endocytosis, creating delivery challenges such as lysosomal escape. She reviewed evidence that EV cargo mediates kidney development and physiology (e.g., transporter proteins, regulation of ENaC activity) and can drive pathology (e.g., hypoxic tubular-cell EV RNA promoting ferroptosis and AKI-to-CKD progression). She summarized the field’s evolution, regulatory expectations (GMP manufacture, characterization, potency, targeting, immunogenicity, dosing), and early clinical trials suggesting general safety but mixed efficacy.<br /><br />Dr. Benedetta Bussolati focused on podocyte targeting and nephrotic syndrome. Using a glomerular “chip” model, her group showed EVs delivered from the endothelial side can reach podocytes and transfer RNA. In adriamycin nephropathy, MSC-derived EVs reduced proteinuria and restored podocyte ultrastructure. She then presented kidney progenitor-derived EVs (from preterm neonatal urine progenitors) that improved permeability in steroid-resistant nephrotic syndrome podocytes, implicating SUMOylation pathways (SUMO1/SUMO2). She also described engineering red blood cell EVs with a Klotho-derived peptide to inhibit TGF-β signaling and reduce fibrotic markers.<br /><br />Dr. Laura Perin presented amniotic fluid stem cell EVs for Alport syndrome, highlighting glomerular endothelial injury and a mechanism involving VEGF pathway modulation. EV cargo miR-93 was critical for VEGF receptor expression, VEGF “trapping,” endothelial repair, and in vivo benefit; knocking down miR-93 abolished efficacy. She detailed translation work: clone-to-clone consistency, low immunogenicity signals, scalable bioreactor production with tangential flow filtration/size exclusion chromatography, and podocyte-targeted EV surface modification to increase selective uptake and functional benefit in chip models.<br /><br />Dr. Marvin Droste discussed key roadblocks to MSC-EV clinical implementation: incomplete mechanistic understanding, limited renal biodistribution in health (liver/spleen uptake), context-dependent effects, and major batch variability requiring validated potency assays. He emphasized the need for standardized GMP-scale manufacturing and purification, and industry partnerships, noting progress from MSC clinical approvals and rigorous trial designs in CKD.

Asset Subtitle

Moderator(s): Uta Erdbruegger, Ewout Hoorn

Presentation(s):

Why Extracellular Vesicles? - Monica Ng
Kidney Progenitor-Derived Extracellular Vesicles for Nephrotic Syndrome Therapy - Benedetta Bussolati
Extracellular Vesicles for Kidney Repair in Alport Syndrome - Laura Perin
Roadblocks of Implementing Mesenchymal Stem Cell Extracellular Vesicles - Marvin Droste

Meta Tag

Date 11/8/2025

Pathway 1 Kidney Biology and Physiology

Pathway 2 CKD Non-Dialysis

Session ID 507275

Keywords

extracellular vesicles (EVs)

exosomes

ectosomes (microvesicles)

apoptotic bodies

kidney disease therapeutics

acute kidney injury (AKI)

chronic kidney disease (CKD)

AKI-to-CKD progression

ferroptosis

podocyte targeting

nephrotic syndrome

mesenchymal stromal cell (MSC)-derived EVs

Alport syndrome

VEGF pathway modulation

GMP manufacturing and potency assays