Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke
Open accessAbstract
Bone marrow stromal cells (BMSCs) facilitate functional recovery in rats after stroke when administered acutely (1 day) or subacutely (7 days). In this study, we postponed the time of cell transplantation to 1 month after stroke. Female retired breeder rats were subjected to 2 h of middle cerebral artery occlusion (MCAo). Male BMSCs (3×10 6) or phosphate-buffered saline were administered intravenously, and the animals were killed 3 months later. An additional population of nontreated rats was killed at 1 month after MCAo. Significant recovery of behavior was found in BMSC-treated rats beginning at 1 month after cell injection in the modified neurologic severity score test and the adhesive-removal test compared with control animals ( P < 0.05). In situ hybridization showed that BMSCs survived and preferentially localized to the ipsilateral hemisphere. Double staining revealed that approximately 13% and 6% Y-chromosome-positive cells expressed the astrocyte marker, glial fibrillary acidic protein, and the neuronal marker, microtubule-associated protein-2, respectively. In addition, BMSC treatment reduced scar thickness, and increased the number of proliferating cells and oligodendrocyte precursor cells along the subventricular zone in the ipsilateral hemisphere. Expression of the chemokine stromal-cell-derived factor-1 (SDF-1) was significantly increased along the ischemic boundary zone compared with the corresponding areas in the contralateral hemisphere at 1 month and 4 months ( P < 0.01) after stroke. The SDF-1 receptor, CXC-chemokine receptor-4 (CXCR4), was expressed in BMSCs both in vitro and in vivo. Our data show that the time window of BMSC therapy is at least 1 month after stroke; the interaction of SDF-1/CXCR4 may contribute to the trafficking of transplanted BMSCs.
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In rodents, beneficial effects of neurorestorative treatments were reported even when treatments were initiated days, weeks, or months after stroke.
“In rodents, beneficial effects were reported even when treatments were initiated days, weeks, or months after stroke.14–20”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [18]
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Self-citation
- Authors
- Shen, L. H., Li, Y., Chen, J., Zacharek, A., Gao, Q., Kapke, A., Lu, M., Raginski, K., Vanguri, P., Smith, A., & Chopp, M.
- Affiliations
- Henry Ford Health (US)
- Corresponding author
- Chopp, Michael
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2007-01
- Volume
- 27
- Issue
- 1
- Pages
- 6-13
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W2080638375
- Cited by
- 353
- References
- 27
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 15 · 2019: 12 · 2018: 17 · 2017: 13 · 2016: 27 · 2015: 26 · 2014: 29 · 2013: 29 · 2012: 22
- FWCI
- 11.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P01NS23393, R01NS045041, P01NS023393, P01NS042345, R01 NS45041)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Keywords
- mesenchymal stem cells, stroke, middle cerebral artery occlusion, functional recovery, SDF-1/CXCR4, cell trafficking, oligodendrocyte precursor cells, subventricular zone, glial scar, astrocytes, MAP2
- MeSH terms
- Animals, Behavior, Animal, Female, Immunoglobulins, Immunohistochemistry, Male, Membrane Glycoproteins, Physical Stimulation, Psychomotor Performance, Biomarkers, Bone Marrow Transplantation, Stromal Cells, Rats, Wistar, In Situ Hybridization, Fluorescence, Receptors, CXCR4, Chemokines, CXC, Reverse Transcriptase Polymerase Chain Reaction, Infarction, Middle Cerebral Artery, Stroke, Rats, Chemokine CXCL12
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