Abstract | BACKGROUND:
Stem cell transplantation has been documented to promote functional recovery in animal models of stroke; however, the underlying mechanisms are not yet fully understood. As netrin-1 and its receptor deleted in colorectal cancer (DCC) are important regulators in neuronal and vascular activities, the present study attempted to explore whether netrin-1 and DCC are involved in the neuroprotection of stem cell-based therapies in a rat ischemic stroke model. METHODS: Adult male Sprague-Dawley rats were subjected to a transient middle cerebral artery occlusion (MCAO) and subsequently received an intra-arterial injection of 2 × 106 PKH26-labeled adipose-derived stem cells (ADSCs) or saline 24 h later. Neurological function was evaluated by behavioral tests before the rats were sacrificed at days 7 and 14 after MCAO. The migration of ADSCs and regeneration of neuronal fibers and blood vessels were determined by immunofluorescence staining. The expression of netrin-1 and DCC was analyzed by Western blot and immunofluorescence staining. RESULTS: ADSC transplantation significantly improved the neurological recovery at days 7 and 14, and noticeably promoted the regeneration of neuronal fibers and blood vessels in the peri- infarct cortex at day 14. PKH26-labeled ADSCs located mainly in the peri- infarct area at days 7 and 14. In ADSC-treated rats, the expression of netrin-1 and DCC significantly increased in the peri- infarct cortex at days 7 and 14. Immunofluorescence staining showed that netrin-1 was mainly expressed by neuronal perikaryal in the peri- infarct cortex, and DCC was mainly expressed by neuronal fibers and was present around the blood vessels in the peri- infarct cortex. CONCLUSIONS: These findings suggest that ADSC transplantation facilitates the regeneration of neuronal fibers and blood vessels in the peri- infarct cortex and improves neurological functions, which may be attributed, at least in part, to the involvement of upregulated netrin-1 and DCC in the remodeling of neuronal and vascular networks in the peri- infarct cortex.
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Authors | Huan Huang, Fan Lin, Jingjing Jiang, Yan Chen, Ainong Mei, Pengli Zhu |
Journal | Stem cell research & therapy
(Stem Cell Res Ther)
Vol. 8
Issue 1
Pg. 223
(10 10 2017)
ISSN: 1757-6512 [Electronic] England |
PMID | 29017609
(Publication Type: Journal Article)
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Chemical References |
- DCC Receptor
- Dcc protein, rat
- Netrin-1
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Topics |
- Adipose Tissue
(cytology)
- Animals
- Cell Movement
- Cells, Cultured
- Cerebral Cortex
(metabolism)
- DCC Receptor
(genetics, metabolism)
- Infarction, Middle Cerebral Artery
(therapy)
- Male
- Mesenchymal Stem Cell Transplantation
(methods)
- Mesenchymal Stem Cells
(cytology, metabolism, physiology)
- Nerve Regeneration
- Netrin-1
(genetics, metabolism)
- Rats
- Rats, Sprague-Dawley
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