Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblasts

Abstract The physiologic relationship between the brain and heart is emerging as a novel therapeutic target for clinical intervention for acute myocardial infarction. In the adult human brain, vestigial neuronal progenitor stem cells contribute to neuronal repair and recovery following cerebral isch...

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Main Authors: Oiva Arvola, Virpi Stigzelius, Minna Ampuja, Riikka Kivelä
Format: Article
Language:English
Published: BMC 2025-02-01
Series:BMC Neuroscience
Subjects:
Online Access:https://doi.org/10.1186/s12868-025-00931-1
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author Oiva Arvola
Virpi Stigzelius
Minna Ampuja
Riikka Kivelä
author_facet Oiva Arvola
Virpi Stigzelius
Minna Ampuja
Riikka Kivelä
author_sort Oiva Arvola
collection DOAJ
description Abstract The physiologic relationship between the brain and heart is emerging as a novel therapeutic target for clinical intervention for acute myocardial infarction. In the adult human brain, vestigial neuronal progenitor stem cells contribute to neuronal repair and recovery following cerebral ischemic injury, an effect modulated by secreted exosomes. Ischemia conditioned neuronal cell derived supernatant and experimental stroke has been shown to be injurious to the heart. However, whether unconditioned neuronal progenitor cell derived-exosomes can instead protect myocardium represents a profound research gap. We investigated the effects of unconditioned neural stem cell derived exosomes as post-injury treatment for cardiomyoblasts from three neuronal culture conditions; adherent cultures, neurosphere cultures and bioreactor cultures. Small extracellular vesicles were enriched with serial ultracentrifugation, validated via nanoparticle tracking analysis, transmission electron microscopy and Western blot analysis prior to utilization as post-injury treatment for H9c2 cardiomyoblasts following oxygen and glucose deprivation. LDH assay was used to assess viability and Seahorse XF high-resolution respirometry analyzer to investigate post-injury cardiomyocyte bioenergetics. We found no evidence that unconditioned neural stem cell derived exosomes are cardiotoxic nor cardioprotective to H9c2 cardiomyoblasts following ischemia-reperfusion injury. Based on our findings, utilizing unconditioned neural stem cell derived exosomes as post-injury treatment for other organs should not have adverse effects to the damaged cardiac cells.
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series BMC Neuroscience
spelling doaj-art-77f2dd18948248919c8d79a24b02da412025-02-09T12:14:06ZengBMCBMC Neuroscience1471-22022025-02-0126111410.1186/s12868-025-00931-1Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblastsOiva Arvola0Virpi Stigzelius1Minna Ampuja2Riikka Kivelä3Division of Intensive Care, Department of Anaesthesiology and Intensive Care, University of Helsinki and Helsinki University HospitalStem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of HelsinkiStem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of HelsinkiStem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of HelsinkiAbstract The physiologic relationship between the brain and heart is emerging as a novel therapeutic target for clinical intervention for acute myocardial infarction. In the adult human brain, vestigial neuronal progenitor stem cells contribute to neuronal repair and recovery following cerebral ischemic injury, an effect modulated by secreted exosomes. Ischemia conditioned neuronal cell derived supernatant and experimental stroke has been shown to be injurious to the heart. However, whether unconditioned neuronal progenitor cell derived-exosomes can instead protect myocardium represents a profound research gap. We investigated the effects of unconditioned neural stem cell derived exosomes as post-injury treatment for cardiomyoblasts from three neuronal culture conditions; adherent cultures, neurosphere cultures and bioreactor cultures. Small extracellular vesicles were enriched with serial ultracentrifugation, validated via nanoparticle tracking analysis, transmission electron microscopy and Western blot analysis prior to utilization as post-injury treatment for H9c2 cardiomyoblasts following oxygen and glucose deprivation. LDH assay was used to assess viability and Seahorse XF high-resolution respirometry analyzer to investigate post-injury cardiomyocyte bioenergetics. We found no evidence that unconditioned neural stem cell derived exosomes are cardiotoxic nor cardioprotective to H9c2 cardiomyoblasts following ischemia-reperfusion injury. Based on our findings, utilizing unconditioned neural stem cell derived exosomes as post-injury treatment for other organs should not have adverse effects to the damaged cardiac cells.https://doi.org/10.1186/s12868-025-00931-1Neural stem cellsExosomeSmall EVStrokeMyocardial infarctionIR-injury
spellingShingle Oiva Arvola
Virpi Stigzelius
Minna Ampuja
Riikka Kivelä
Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblasts
BMC Neuroscience
Neural stem cells
Exosome
Small EV
Stroke
Myocardial infarction
IR-injury
title Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblasts
title_full Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblasts
title_fullStr Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblasts
title_full_unstemmed Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblasts
title_short Neural progenitor cell-derived exosomes in ischemia/reperfusion injury in cardiomyoblasts
title_sort neural progenitor cell derived exosomes in ischemia reperfusion injury in cardiomyoblasts
topic Neural stem cells
Exosome
Small EV
Stroke
Myocardial infarction
IR-injury
url https://doi.org/10.1186/s12868-025-00931-1
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AT virpistigzelius neuralprogenitorcellderivedexosomesinischemiareperfusioninjuryincardiomyoblasts
AT minnaampuja neuralprogenitorcellderivedexosomesinischemiareperfusioninjuryincardiomyoblasts
AT riikkakivela neuralprogenitorcellderivedexosomesinischemiareperfusioninjuryincardiomyoblasts