Epidermal neural crest stem cell transplantation as a promising therapeutic strategy for ischemic stroke
Open Access
- 1 July 2020
- journal article
- research article
- Published by Wiley in CNS Neuroscience & Therapeutics
- Vol. 26 (7), 670-681
- https://doi.org/10.1111/cns.13370
Abstract
Introduction Cell-based therapy is considered as promising strategy to cure stroke. However, employing appropriate type of stem cell to fulfill many therapeutic needs of cerebral ischemia is still challenging. In this regard, the current study was designed to elucidate therapeutic potential of epidermal neural crest stem cells (EPI-NCSCs) compared to bone marrow mesenchymal stem cells (BM-MSCs) in rat model of ischemic stroke. Methods Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) for 45 minutes. Immediately after reperfusion, EPI-NCSCs or BM-MSCs were transplanted via intra-arterial or intravenous route. A test for neurological function was performed before ischemia and 1, 3, and 7 days after MCAO. Also, infarct volume ratio and relative expression of 15 selected target genes were evaluated 7 days after transplantation. Results EPI-NCSCs transplantation (both intra-arterial and intravenous) and BM-MSCs transplantation (only intra-arterial) tended to result in a better functional outcome, compared to the MCAO group; however, this difference was not statistically significant. The infarct volume ratio significantly decreased in NCSC-intra-arterial, NCSC-intravenous and MSC-intra-arterial groups compared to the control. EPI-NCSCs interventions led to higher expression levels of Bdnf, nestin, Sox10, doublecortin, beta-III tubulin, Gfap, and interleukin-6, whereas neurotrophin-3 and interleukin-10 were decreased. On the other hand, BM-MSCs therapy resulted in upregulation of Gdnf, beta-III tubulin, and Gfap and down-regulation of neurotrophin-3, interleukin-1, and interleukin-10. Conclusion These findings highlight the therapeutic effects of EPI-NCSCs transplantation, probably through simultaneous induction of neuronal and glial formation, as well as Bdnf over-expression in a rat model of ischemic stroke.Funding Information
- Shiraz University of Medical Sciences (1396‐01‐94‐15586)
- Iran National Science Foundation (96016991)
- Deutsche Forschungsgemeinschaft (Ne465/27‐1, Ne465/31‐1)
- Iran's National Elites Foundation
- International Brain Research Organization
This publication has 61 references indexed in Scilit:
- Ablation of Neurogenesis Attenuates Recovery of Motor Function after Focal Cerebral Ischemia in Middle-Aged MicePLOS ONE, 2012
- Intraoperative Stem Cell TherapyAnnual Review of Biomedical Engineering, 2012
- Human Epidermal Neural Crest Stem Cells (hEPI-NCSC)—Characterization and Directed Differentiation into Osteocytes and MelanocytesStem Cell Reviews and Reports, 2011
- Sox10 directs neural stem cells toward the oligodendrocyte lineage by decreasing Suppressor of Fused expressionProceedings of the National Academy of Sciences of the United States of America, 2010
- Epidermal Neural Crest Stem Cell (EPI-NCSC)—Mediated Recovery of Sensory Function in a Mouse Model of Spinal Cord InjuryStem Cell Reviews and Reports, 2010
- Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in miceProceedings of the National Academy of Sciences of the United States of America, 2010
- Optimizing the success of cell transplantation therapy for strokeNeurobiology of Disease, 2010
- Validation of housekeeping genes for quantitative real-time PCR in in-vivo and in-vitro models of cerebral ischaemiaBMC Molecular Biology, 2009
- Identification of Ischemic Regions in a Rat Model of StrokePLOS ONE, 2009
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001