ArticlePLoS biology2021
Neural stem cells traffic functional mitochondria via extracellular vesicles.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
160 citing papers in PubMed, 231 citations in OpenAlex.
- Cellular Mechanisms Enabling Mitochondria Transfer and Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Sequential-RSC pharmaceutics · 2026Article
- Intercellular Mitochondrial Transfer in the Nervous System: Roles of Tunneling Nanotubes, Mitochondrial Extracellular Vesicles, and Neuroimmune Bioenergetic Interactions.Molecular neurobiology · 2026Review
- Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.International journal of molecular sciences · 2026Review
- Platelet-derived mitochondrial transfer in cancer metastasis: mechanisms, functional consequences, and translational opportunities.Clinical & experimental metastasis · 2026Review
- Mesenchymal Stromal Cell-Derived Extracellular Vesicles Mediate Mitochondrial Delivery in Injury: Mechanistic Insights, Evidentiary Tiers, and Translational Challenges.Stem cell reviews and reports · 2026Review
- ID3 -depleted human induced pluripotent stem cell-derived neural stem/progenitor cells promote neurorepair.Neural regeneration research · 2026Article
- The central role of mitochondrial dysfunction in neurodegeneration: implications for therapy.Molecular and cellular biochemistry · 2026Review
- Transcriptomic analysis reveals that neural stem cell-derived exosomes regulate the HMGB1/TLR2 signaling axis to promote astrocytic differentiation and mitochondrial biogenesis in the repair of radiation-induced blood-brain barrier damage.Cell death discovery · 2026Article
- MSC-Derived Extracellular Vesicles Mitigate Ischemia-Induced Energetic Dysfunction During Ex Situ Perfusion of Rat Livers.Antioxidants (Basel, Switzerland) · 2026Article
- Engineering Extracellular Vesicles for Anti-Aging Therapy: Mechanisms, Applications, and Perspectives.Aging cell · 2026Review
- Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.Biomolecules · 2026Review
- The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models.International journal of molecular sciences · 2026Review
- Neuromodulatory role and therapeutic potential of N 6 -methyladenosine RNA methylation in neurodegenerative diseases.Neural regeneration research · 2026Article
- From insights to innovations: evaluating preclinical paradigms in demyelinating disease therapeutics.Lab animal · 2026Review
- Mitochondria transfer in neurological disorders: the key role of neuroglia.Molecular neurodegeneration · 2026Review
- Stem Cell-Derived Exosomes Regulate Mitochondrial Function: A Novel Strategy for Parkinson's Disease Therapy.Molecular neurobiology · 2026Review
- Review
- Mitochondrial-Immune Dysfunction in MS: Therapeutic Potential of EV-Mediated Transfer.Cellular and molecular neurobiology · 2026Review
- Two Routes for Removing Unhealthy Mitochondria: Degradation and Secretion.Circulation research · 2026Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors at 6 institutions in 5 countries.
Funding
Abstract
Neural stem cell (NSC) transplantation induces recovery in animal models of central nervous system (CNS) diseases. Although the replacement of lost endogenous cells was originally proposed as the primary healing mechanism of NSC grafts, it is now clear that transplanted NSCs operate via multiple mechanisms, including the horizontal exchange of therapeutic cargoes to host cells via extracellular vesicles (EVs). EVs are membrane particles trafficking nucleic acids, proteins, metabolites and metabolic enzymes, lipids, and entire organelles. However, the function and the contribution of these cargoes to the broad therapeutic effects of NSCs are yet to be fully understood. Mitochondrial dysfunction is an established feature of several inflammatory and degenerative CNS disorders, most of which are potentially treatable with exogenous stem cell therapeutics. Herein, we investigated the hypothesis that NSCs release and traffic functional mitochondria via EVs to restore mitochondrial function in target cells. Untargeted proteomics revealed a significant enrichment of mitochondrial proteins spontaneously released by NSCs in EVs. Morphological and functional analyses confirmed the presence of ultrastructurally intact mitochondria within EVs with conserved membrane potential and respiration. We found that the transfer of these mitochondria from EVs to mtDNA-deficient L929 Rho0 cells rescued mitochondrial function and increased Rho0 cell survival. Furthermore, the incorporation of mitochondria from EVs into inflammatory mononuclear phagocytes restored normal mitochondrial dynamics and cellular metabolism and reduced the expression of pro-inflammatory markers in target cells. When transplanted in an animal model of multiple sclerosis, exogenous NSCs actively transferred mitochondria to mononuclear phagocytes and induced a significant amelioration of clinical deficits. Our data provide the first evidence that NSCs deliver functional mitochondria to target cells via EVs, paving the way for the development of novel (a)cellular approaches aimed at restoring mitochondrial dysfunction not only in multiple sclerosis, but also in degenerative neurological diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.