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Cited by 10Extracellular vesicles in diseaseMesenchymal stem cell researchStroke Rehabilitation and Recovery

Transplantation of exosomes derived from human Wharton’s jelly mesenchymal stromal cells enhances functional Improvement in Stroke Rats

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Chiu, Yu-Sung, Wu, Kuo-Jen, Yu, Seong-Jin, Wu, Kun-Lieh, Hsieh, Chang-Yi, Chou, Yu-Sheng, Chen, Kuan-Yu, Wang, Yu-Syuan +7 more·2024·Cell Transplantation
DOI 10.1177/09636897241296366PMC PMC11613244
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Abstract

Cerebral ischemic stroke is a major cerebrovascular disease and the leading cause of adult disability. We and others previously demonstrated that transplantation of human Wharton’s jelly mesenchymal stromal cells (WJ-MSCs) attenuated neuronal damage and promoted functional improvement in stroke animals. This study aimed to investigate the protective effects of human WJ-MSC exosome (Exo) transplant in cellular and rat models of cerebral stroke. Administration of Exo significantly antagonized glutamate-mediated neuronal loss and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-X nick end labeling (TUNEL) in rat primary cortical neuronal cultures. Adult male rats underwent a 60-min middle cerebral artery occlusion (MCAo); Exo or vehicle was injected through the tail vein 5–10 min after the MCAo. Two days later, the rats underwent a series of behavioral tests. Stroke rats receiving Exo developed a significant improvement in locomotor function and forelimb strength while reductions in body asymmetry and Bederson’s neurological score. After the behavioral test, brain tissues were harvested for histological and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses. Animals receiving Exo had less infarction volume, measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Transplantation of Exo increased the expression of protective neurotrophic factors (BMP7, GDNF) and anti-apoptotic factors (Bcl2, Bcl-xL) in the ischemic brain. These findings suggest that early post-treatment with WJ-MSC Exo, given non-invasively through the vein, improved functional recovery and reduced brain damage in the stroke brain.

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  • Isolator-based systems can facilitate production of clinically applicable EVs with consistent quality and safety.

    “The resulting exosomes exhibited significant neuroprotective effects in vitro and in vivo, underscoring how isolator-based systems can facilitate the production of clinically applicable EVs with consistent quality and safety (Chiu et al., 2024).”

    From Isolator-based point-of-care manufacturing: a practical solution for GMP-compliant cell and extracellular vesicles therapy production (2025) · cites this paper as Chiu et al., 2024

    The Materials and Methods (Exosome Purification; page unavailable) describe filtration and spin-column purification, not an isolator-based production system. The Discussion (page unavailable) says clinical safety and regulatory issues still require evaluation; our copy does not address whether isolator-based systems yield EVs of consistent quality and safety. Searched for isolator systems, clinical-grade production, and quality control. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Chiu, Y.-S., Wu, K.-J., Yu, S.-J., Wu, K.-L., Hsieh, C.-Y., Chou, Y.-S., Chen, K.-Y., Wang, Y.-S., Bae, E.-K., Hung, T.-W., Lin, S.-H., Lin, C.-H., Hsu, S.-C., Wang, Y., & Chen, Y.-H.
Affiliations
  • YJ Biotechnology Co., Ltd., New Taipei City, Taiwan
  • China Medical University (TW)
  • National Health Research Institutes (TW)
  • Fu Jen Catholic University (TW)
  • Kaohsiung Medical University (TW)
Corresponding author
Chen, Yun-Hsiang
ORCID
Venue
Cell Transplantation
Publisher
SAGE Publications
Published
2024-01
Volume
33
Pages
9636897241296366-9636897241296366
ISSN
  • 0963-6897 (ISSN-L)
  • 1555-3892
DOI
10.1177/09636897241296366
PMC
PMC11613244
OpenAlex
W4404971131
Cited by
10
References
7
Citations by year
2026: 4 · 2025: 6
FWCI
1.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Transplantation (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • NHRI Institutional Repository (submittedVersion)
Funders
  • YJ Biotechnology Co. Ltd. (C12-018, FJCU-7100491)
  • National Science and Technology Council (MOST 111-2314-B-030-007, NSTC 112-2314-B-030-009)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
Keywords
exosomes, Wharton's jelly mesenchymal stromal cells, ischemic stroke, cell-free therapy, middle cerebral artery occlusion, neuroprotection, neuronal apoptosis, glutamate excitotoxicity, neurotrophic factors, BMP-7, glial cell line-derived neurotrophic factor, Bcl-2, Bcl-xL, infarct size, functional recovery
MeSH terms
Animals, Disease Models, Animal, Humans, Male, Neurons, Rats, Sprague-Dawley, Recovery of Function, Infarction, Middle Cerebral Artery, Stroke, Mesenchymal Stem Cell Transplantation, Rats, Exosomes, Mesenchymal Stem Cells, Wharton Jelly

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