EXOSOME THERAPY AND TREATMENT FOR STROKE

SELECTED ARTICLES

1. Stem Cell-Derived Exosomes as Treatment for Stroke: a Systematic Review

Dehghani et al., Stem Cell Reviews and Reports, 2021 SpringerLink+1

  • What they did: Systematic review of animal studies using stem-cell–derived exosomes as stroke therapy (searched PubMed, Scopus, Web of Science up to April 2020; quality graded with STAIR criteria).

  • Key findings: Across preclinical models, exosomes from diverse stem cell sources (mostly MSCs) consistently improved neurological function, reduced infarct volume, and enhanced neurogenesis and angiogenesis. Mechanisms involved anti-inflammatory effects, reduced apoptosis, and promotion of axonal remodeling.

  • Takeaway: Stem-cell exosomes reproduce many benefits of stem cell therapy with potentially lower risks (e.g., less tumorigenicity and embolic risk), but the evidence is still preclinical and heterogeneous. The authors emphasize the need for standardized dosing, timing, and characterization to move toward clinical trials. SpringerLink+1

2. Exosomes-Based Therapy of Stroke, an Emerging Approach Toward Recovery

Seyedaghamiri et al., Cell Communication and Signaling, 2022 SpringerLink

  • What they did: Narrative review on how exosomes might overcome limitations of current stroke therapies (tPA, thrombectomy, and cell therapy).

  • Key findings:

    • Outlines stroke pathophysiology (excitotoxicity, inflammation, oxidative stress, mitochondrial dysfunction) and the limited window for reperfusion therapies.

    • Explains exosome biogenesis, cargo (miRNAs, proteins, lipids), and their roles in neuroprotection, angiogenesis, neurogenesis, immune modulation, and remyelination.

    • Highlights advantages over stem cells (nano-size, better BBB penetration, lower risk of emboli or tumors) and potential as both biomarkers and therapeutics.

    • Notes concerns: exosome heterogeneity, allogeneic/xenogeneic immune responses, thrombosis/infection risk, and technical challenges in isolation and standardization.

  • Takeaway: Exosomes are positioned as a promising “cell-free” alternative or adjunct to stem cell therapy for stroke, but translation requires solving manufacturing, safety, and dosing issues. SpringerLink

3. Extracellular Vesicles in Regeneration and Rehabilitation Recovery after Stroke

Gualerzi et al., Biology, 2021 MDPI

  • What they did: Review linking extracellular vesicles (EVs), especially exosomes, to regenerative rehabilitation strategies after stroke.

  • Key findings:

    • EVs in blood and other fluids can serve as dynamic biomarkers of brain injury, inflammation, and recovery, potentially enabling “rehabilomics” (personalized rehab based on molecular profiling).

    • Stem-cell–derived and other therapeutic EVs can promote brain remodeling—supporting angiogenesis, neurogenesis, synaptic plasticity, and modulation of neuroinflammation.

    • Preclinical data show EVs can enhance recovery when combined with rehabilitation (e.g., task-specific training), suggesting synergy between biological repair and activity-based plasticity.

    • The field is early; robust biomarkers of recovery and well-designed clinical trials are still lacking.

  • Takeaway: EVs are not just candidate therapies, but also tools to monitor and personalize rehabilitation after stroke. Combining EV therapy with advanced rehab protocols may be especially powerful. MDPI

4. Exosomes in Stroke Pathogenesis and Therapy

Zhang & Chopp, Journal of Clinical Investigation, 2016 JCI+1

  • What they did: Early, influential review on exosomes in the pathogenesis and recovery phases of stroke.

  • Key findings:

    • Stroke recovery is driven by coordinated remodeling of the neurovascular unit (endothelium, neurons, glia, extracellular matrix) and neural stem cells.

    • Exosomes act as key communication vehicles among these components, carrying proteins, lipids, and miRNAs that regulate angiogenesis, neurogenesis, oligodendrogenesis, synaptic plasticity, and glial responses.

    • Exosomal miRNAs (e.g., miR-15a, miR-17-92, miR-27a) are highlighted as regulators of angiogenesis, remyelination, and axonal growth.

    • Discusses therapeutic potential of exosomes derived from mesenchymal stem cells (MSCs) and hematopoietic stem cells as a cell-free regenerative approach.

  • Takeaway: This paper framed exosomes as central orchestrators of post-stroke brain remodeling and helped launch the concept of exosome-based stroke therapy. JCI+1

5. Potential Role of Exosomes in Ischemic Stroke Treatment

Jiang et al., Biomolecules, 2022 MDPI

  • What they did: Comprehensive review of exosomes in ischemic stroke, focusing on mechanisms and therapeutic applications.

  • Key findings:

    • Details how ischemia alters exosome production and cargo in neurons, glia, and endothelial cells, making exosomes both disease mediators and therapeutic targets.

    • Summarizes preclinical evidence that stem-cell–derived exosomes (especially bone-marrow MSC exosomes) enhance angiogenesis, neurogenesis, oligodendrogenesis, and anti-apoptotic pathways, improving functional outcomes in animal stroke models.

    • Highlights specific exosomal miRNAs (e.g., miR-21-3p, miR-134, miR-184, miR-210) that reduce ischemic injury and support brain repair.

    • Discusses route of administration, biodistribution, safety, and engineering strategies (e.g., loading therapeutic miRNAs or drugs into exosomes).

  • Takeaway: Exosomes are portrayed as a multi-mechanistic platform for ischemic stroke therapy; optimizing cargo, delivery route, and standardization is essential for translation. MDPI+1

6. Exosomes: The Next-Generation Therapeutic Platform for Ischemic Stroke

Yin et al., Neural Regeneration Research, 2025 PubMed

  • What they did: Recent review positioning exosomes as a “next-generation” stroke therapy, with emphasis on engineered exosomes and nanotechnology.

  • Key findings:

    • Reiterates that current stroke treatments rarely achieve full neurological recovery and are limited by narrow time windows.

    • Reviews exosome advantages: low immunogenicity, stability, high delivery efficiency, ability to cross the BBB, and compatibility with bioengineering.

    • Summarizes exosome-mediated neuroprotective actions: anti-inflammatory, anti-apoptotic, regulation of autophagy, promotion of angiogenesis and neurogenesis, and reduction of glial scar formation.

    • Highlights engineered exosomes (e.g., drug-loaded exosomes, exosome-eluting stents, exosomes combined with edaravone or tPA) as ways to improve targeting and efficacy while lowering required doses.

    • Stresses major bottlenecks: lack of standardized characterization, limited scalable and efficient isolation methods, and need for unified workflows for clinical use.

  • Takeaway: Exosomes, especially when engineered, are framed as a versatile therapeutic and delivery platform for ischemic stroke, but regulatory-grade manufacturing and standardization remain key hurdles. PubMed

7. A Narrative Review on Exosomes Therapeutics in Stroke: Advancing Neuroprotection and Regeneration

Raza et al., Neuroscience, 2025 PubMed

  • What they did: Narrative review focusing on exosomes as neuroprotective and regenerative agents in ischemic stroke, with an emphasis on neuroinflammation and oxidative stress.

  • Key findings:

    • Describes how exosomes modulate immune responses, reduce oxidative stress, and support neuronal repair in stroke models.

    • Emphasizes cargo-driven mechanisms: exosomal miRNAs (e.g., miR-124, miR-21), stress proteins (e.g., HSP70), and bioactive lipids that contribute to neuroprotection and neurogenesis.

    • Integrates data from both preclinical and early clinical/ translational studies on immune modulation and neuroprotection.

    • Argues that exosome therapies may offer safety and stability advantages over whole-cell therapies (better storage, less tumorigenic risk, potentially simpler logistics).

    • Outlines translational challenges: isolation/standardization, targeting, dosing, and ensuring safety.

  • Takeaway: Exosomes are presented as promising next-generation neuroprotective agents that act largely through immune and oxidative-stress modulation, but the field is still in a pre-clinical/early-translational stage. PubMed+1

8. Mesenchymal Stem Cell-Derived Exosomes: Shaping the Next Era of Stroke Treatment

Waseem et al., Neuroprotection, 2023 PubMed+1

  • What they did: Focused review on MSC-derived exosomes (MSC-Exos) in ischemic stroke.

  • Key findings:

    • MSC-Exos are highlighted as particularly attractive because they are low-immunogenic, cross the BBB, and efficiently deliver therapeutic cargo.

    • They exert combined effects: neuroprotection, pro-angiogenic and pro-neurogenic actions, modulation of inflammatory responses, and attenuation of cell-death pathways—supporting functional recovery in experimental stroke.

    • Discusses the potential of MSC-Exos as diagnostic biomarkers as well as therapeutics.

    • Identifies major limitations: heterogeneity of exosome populations, difficulties in standardizing isolation/purification, and unresolved questions about optimal dosing, route of delivery, and targeting.

    • Calls for improved production workflows, robust evaluation criteria, and scalable isolation technologies to make MSC-Exos clinically practical.

  • Takeaway: MSC-derived exosomes are positioned as a leading candidate among exosome-based approaches for stroke, offering a cell-free MSC therapy alternative with broad mechanistic benefits but significant technical hurdles to overcome. PubMed+1

Reference List:

  1. Dehghani L, Hashemi SM, Saadatnia M, et al. Stem cell-derived exosomes as treatment for stroke: a systematic review. Stem Cell Rev Rep. 2021;17(2):428-438. doi:10.1007/s12015-020-10024-7 SpringerLink+1

  2. Seyedaghamiri F, Salimi L, Ghaznavi D, Sokullu E, Rahbarghazi R. Exosomes-based therapy of stroke, an emerging approach toward recovery. Cell Commun Signal. 2022;20(1):110. doi:10.1186/s12964-022-00919-y SpringerLink

  3. Gualerzi A, Picciolini S, Rodà F, Bedoni M. Extracellular vesicles in regeneration and rehabilitation recovery after stroke. Biology (Basel). 2021;10(9):843. doi:10.3390/biology10090843 MDPI

  4. Zhang ZG, Chopp M. Exosomes in stroke pathogenesis and therapy. J Clin Invest. 2016;126(4):1190-1197. doi:10.1172/JCI81133 JCI+1

  5. Jiang L, Chen W, Ye J, Wang Y. Potential role of exosomes in ischemic stroke treatment. Biomolecules. 2022;12(1):115. doi:10.3390/biom12010115 MDPI+1

  6. Yin W, Ma H, Qu Y, et al. Exosomes: the next-generation therapeutic platform for ischemic stroke. Neural Regen Res. 2025;20(5):1221-1235. doi:10.4103/NRR.NRR-D-23-02051 PubMed

  7. Raza ML, Fatima M, Rawalia MA, Raza R. A narrative review on exosomes therapeutics in stroke: advancing neuroprotection and regeneration. Neuroscience. 2025;584:311-322. doi:10.1016/j.neuroscience.2025.08.044 PubMed+1

  8. Waseem A, Saudamini, Haque R, Janowski M, Raza SS. Mesenchymal stem cell-derived exosomes: shaping the next era of stroke treatment. Neuroprotection. 2023;1(2):99-116. doi:10.1002/nep3.30

Devin Wilson, ND

NaturopathiC Doctor

Ashland, Oregon 97520

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