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Cited by 28Mesenchymal stem cell researchStroke Rehabilitation and RecoveryAcute Ischemic Stroke Management

Intracerebral Transplants of GMP-Grade Human Umbilical Cord-Derived Mesenchymal Stromal Cells Effectively Treat Subacute-Phase Ischemic Stroke in a Rodent Model

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Noh, Jeong-Eun, Oh, Seung-Hun, Park, In-Hyun, Song, Jihwan·2020·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2020.546659PMC PMC7546889
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Abstract

In the subacute and chronic phases of stroke, there are currently no effective treatment for functional recovery. Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) are one of the candidate cell sources for the treatment of subacute phase stroke. Therapeutic benefits gained from cell-based therapy largely depend on the migratory capacity, extent of cell engraftment in the target tissues and their paracrine activity. Timing and delivery route of stem cells can also influence the outcome of cell therapy. However, it remains to be elucidated how the different routes of hUC-MSC delivery affect cell replacement and cell-to-cell paracrine effect for functional recovery in the subacute phase of stroke. In this study, we compared therapeutic effects of different delivery routes of Good Manufacturing Practice (GMP)-grade hUC-MSCs in a rodent model of subacute-phase stroke. The 1ⅹ106 hUC-MSCs were injected intravenously (IV) or transplanted intracerebrally (IC) at 1 week after middle cerebral artery occlusion (MCAo) in rats, and the transplanted animals were examined up to 7 weeks after transplantation using various behavioral tests and immunohistochemical analyses. Most IC-transplanted cells survived for short period of time (i.e., less than 4 weeks after transplantation) and disappeared gradually afterwards. The IV-injected cells were not detected in the brain at the same time points (i.e., 3 days, 4 weeks and 7 weeks after injection). Although IC-transplanted cells didn’t survive for long periods of time, they were effective in improving behavioral deficits, reducing infarct volume and glial scar formation, and increasing the number of proliferating neuroblasts in the subventricular zone and cerebral vessel formation in the ischemic penumbra region. However, IV injection was not effective in improving behavioral function and histological parameters at 7 weeks after injection. Taken together, our results suggest that IC transplantation is a preferable route of delivery of hUC-MSCs than IV injection in the subacute-phase stroke.

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  • An intracerebral injection avoids the tissue barrier that the blood-CSF barrier or blood-brain-barrier represents and consequently should lead to significantly higher brain transfection levels by specifically targeting local regions of the brain.

    “An intracerebral injection avoids the tissue barrier that blood-cerebrospinal fluid (CSF) barrier or blood-brain-barrier (BBB) represents, and consequently should lead to significantly higher brain transfection levels by specifically targeting local regions of the brain (4, 20, 22, 26, 27).”

    From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [27]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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Cited by

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Authors
Noh, J.-E., Oh, S.-H., Park, I.-H., & Song, J.
Affiliations
  • CHA University (KR)
  • CHA University Bundang Medical Center (KR)
  • Yale University (US)
Corresponding author
Song, Jihwan
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2020-09-25
Volume
14
Pages
546659-546659
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2020.546659
PMC
PMC7546889
OpenAlex
W3088492415
Cited by
28
References
4
Citations by year
2026: 1 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 4 · 2021: 2
FWCI
1.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Research Foundation of Korea (NRF-2017M3A9B4061407)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
Keywords
intracerebral transplantation, subacute ischemic stroke, cell delivery routes, intravenous injection, middle cerebral artery occlusion, cell engraftment, paracrine effects, functional recovery, infarct size, glial scar, cerebral angiogenesis, ischemic penumbra

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