Background: Acute hypoxic proximal tubule (PT) injury and subsequent maladaptive repair present high mortality and increased risk of acute kidney injury (AKI) - chronic kidney disease (CKD) transition. Human bone marrow mesenchymal stem cell-derived exosomes (hBMMSC-Exos) as potential cell therapeutics can be translated into clinics if drawbacks on safety and efficacy are clarified. Here, we determined the real-time effective dose and treatment window of allogeneic hBMMSC-Exos, evaluated their performance on the structural and functional integrity of 3D microfluidic acute hypoxic PT injury platform.
Methods: hBMMSC-Exos were isolated and characterized. Real-time impedance-based cell proliferation analysis (RTCA) determined the effective dose and treatment window for acute hypoxic PT injury. A 2-lane 3D gravity-driven microfluidic platform was set to mimic PT in vitro. ZO-1, acetylated α-tubulin immunolabelling, and permeability index assessed structural; cell proliferation by WST-1 measured functional integrity of PT.
Results: hBMMSC-Exos induced PT proliferation with ED50 of 172,582 µg/ml at the 26th hour. Hypoxia significantly decreased ZO-1, increased permeability index, and decreased cell proliferation rate on 24-48 h in the microfluidic platform. hBMMSC-Exos reinforced polarity by a 1.72-fold increase in ZO-1, restored permeability by 20/45-fold against 20/155 kDa dextran and increased epithelial proliferation 3-fold compared to control.
Conclusions: The real-time potency assay and 3D gravity-driven microfluidic acute hypoxic PT injury platform precisely demonstrated the therapeutic performance window of allogeneic hBMMSC-Exos on ischemic AKI based on structural and functional cellular data. The novel standardized, non-invasive two-step system validates the cell-based personalized theragnostic tool in a real-time physiological microenvironment prior to safe and efficient clinical usage in nephrology.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11005291 | PMC |
| http://dx.doi.org/10.1186/s13287-024-03674-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Synaptotagmin-1 attenuates myocardial programmed necrosis and ischemia/reperfusion injury through the mitochondrial pathway.
Cell Death Dis
January 2025
Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, and the Department of Physiology, School of Basic Medicine, Shanxi Medical University, Taiyuan, China.
Programmed necrosis/necroptosis greatly contributes to the pathogenesis of cardiac disorders including myocardial infarction, ischemia/reperfusion (I/R) injury and heart failure. However, the fundamental mechanism underlying myocardial necroptosis, especially the mitochondria-dependent death pathway, is poorly understood. Synaptotagmin-1 (Syt1), a Ca sensor, is originally identified in nervous system and mediates synchronous neurotransmitter release.
View Article and Find Full Text PDFIschemic stroke can cause damage to neurons, resulting in neurological dysfunction. The main treatments in the acute phase include intravenous thrombolysis, endovascular stent-assisted vascular thrombectomy and antiplatelet therapy. Due to the limitations of the time window and the risk of early intracranial hemorrhage, finding active treatment plans is crucial for improving therapy.
View Article and Find Full Text PDFPhosphodiesterase inhibition restoreshypoxia-induced cerebrovascular dysfunction subsequent to improved systemic redox homeostasis: A randomized, double-blind, placebo-controlled crossover study.
J Cereb Blood Flow Metab
January 2025
Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontypridd, UK.
To what extent sildenafil, a selective inhibitor of the type-5 phosphodiesterase modulates systemic redox status and cerebrovascular function during acute exposure to hypoxia remains unknown. To address this, 12 healthy males (aged 24 ± 3 y) participated in a randomized, placebo-controlled crossover study involving exposure to both normoxia and acute (60 min) hypoxia (Fi = 0.14), followed by oral administration of 50 mg sildenafil and placebo (double-blinded).
View Article and Find Full Text PDFAcute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells.
Int J Mol Sci
January 2025
Biomedicine Research Center of Strasbourg (CRBS), UR 3072, "Mitochondria, Oxidative Stress and Muscle Plasticity", Faculty of Medicine, University of Strasbourg, 67000 Strasbourg, France.
Peripheral blood mononuclear cells' (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of acute hypoxia on PBMC mitochondrial respiration and ROS production in healthy volunteers exposed to controlled oxygen reduction, achieving an inspired oxygen fraction of 10.5%.
View Article and Find Full Text PDFRadiomics for Predicting the Development of Brain Edema from Normal-Appearing Early Brain-CT After Cardiac Arrest and Return of Spontaneous Circulation.
Diagnostics (Basel)
January 2025
Clinic of Diagnostic and Interventional Radiology, Marburg University Hospital, Philipps-University Marburg, Baldingerstrasse, 35043 Marburg, Germany.
Hypoxic-ischemic brain injury (HIBI) is a feared complication post-cardiac arrest (CA). The timing of brain imaging remains a topic of ongoing debate. Early computed tomography (CT) scans can reveal acute intracranial pathologies but may have limited predictive value due to delayed manifestation of HIBI-related changes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!