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Functional recovery after hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke in rats.
Neuroscience 2011; 175:394-405N

Abstract

Hematic administration of bone marrow-derived mesenchymal stem cells (MSCs) in acute ischemic stroke may not only be an effective reparative treatment but also a brain protective therapy that improves neurological recovery. Our purpose was to study whether either i.v. or intracarotid (i.c.) administration of allogenic MSCs during the acute phase were effective in improving neurological recovery and decreasing brain damage in an experimental rat model. In a model of permanent middle cerebral artery occlusion (pMCAO), we analyzed: neurological evaluation; MSCs migration and implantation; interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels; lesion volume; cell death; cellular proliferation; vascular endothelial growth factor (VEGF) expression and blood vessel number. Regardless of the administration route, treated groups showed better neurological recovery, without significant differences between the two groups. Migration and implantation of MSCs in the lesion area was observed in animals receiving i.c. but not i.v. treatment. The highest cytokine values were observed in the i.v. MSCs and i.c. control groups, and these levels were significantly different from the corresponding i.v. control and i.c. MSCs groups, respectively. In addition, there were significant differences between the i.v. MSCs and i.c. MSCs groups in IL-6 levels. Neither treatment reduced infarction volume. However, cell death, measured as TUNEL+ cells was decreased with significant differences between control groups. BrdU+ cells were also significantly increased in the peri-infarct zone at 14 days. VEGF expression was significantly higher in the i.c. MSCs group than in the i.c. control group and blood vessel number was significantly higher in treated groups than control groups with significant differences in the peri-infarct zone at 14 days. We conclude that allogenic MSCs administration shows therapeutic efficacy in our acute ischemic stroke model. Both routes demonstrably improved neurological recovery and provided brain protection.

Authors+Show Affiliations

Hospital La Paz/Autonoma University School of Medicine, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21144885

Citation

Gutiérrez-Fernández, M, et al. "Functional Recovery After Hematic Administration of Allogenic Mesenchymal Stem Cells in Acute Ischemic Stroke in Rats." Neuroscience, vol. 175, 2011, pp. 394-405.
Gutiérrez-Fernández M, Rodríguez-Frutos B, Alvarez-Grech J, et al. Functional recovery after hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke in rats. Neuroscience. 2011;175:394-405.
Gutiérrez-Fernández, M., Rodríguez-Frutos, B., Alvarez-Grech, J., Vallejo-Cremades, M. T., Expósito-Alcaide, M., Merino, J., ... Díez-Tejedor, E. (2011). Functional recovery after hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke in rats. Neuroscience, 175, pp. 394-405. doi:10.1016/j.neuroscience.2010.11.054.
Gutiérrez-Fernández M, et al. Functional Recovery After Hematic Administration of Allogenic Mesenchymal Stem Cells in Acute Ischemic Stroke in Rats. Neuroscience. 2011 Feb 23;175:394-405. PubMed PMID: 21144885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional recovery after hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke in rats. AU - Gutiérrez-Fernández,M, AU - Rodríguez-Frutos,B, AU - Alvarez-Grech,J, AU - Vallejo-Cremades,M T, AU - Expósito-Alcaide,M, AU - Merino,J, AU - Roda,J M, AU - Díez-Tejedor,E, Y1 - 2010/12/07/ PY - 2010/06/09/received PY - 2010/11/23/revised PY - 2010/11/27/accepted PY - 2010/12/15/entrez PY - 2010/12/15/pubmed PY - 2012/6/2/medline SP - 394 EP - 405 JF - Neuroscience JO - Neuroscience VL - 175 N2 - Hematic administration of bone marrow-derived mesenchymal stem cells (MSCs) in acute ischemic stroke may not only be an effective reparative treatment but also a brain protective therapy that improves neurological recovery. Our purpose was to study whether either i.v. or intracarotid (i.c.) administration of allogenic MSCs during the acute phase were effective in improving neurological recovery and decreasing brain damage in an experimental rat model. In a model of permanent middle cerebral artery occlusion (pMCAO), we analyzed: neurological evaluation; MSCs migration and implantation; interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels; lesion volume; cell death; cellular proliferation; vascular endothelial growth factor (VEGF) expression and blood vessel number. Regardless of the administration route, treated groups showed better neurological recovery, without significant differences between the two groups. Migration and implantation of MSCs in the lesion area was observed in animals receiving i.c. but not i.v. treatment. The highest cytokine values were observed in the i.v. MSCs and i.c. control groups, and these levels were significantly different from the corresponding i.v. control and i.c. MSCs groups, respectively. In addition, there were significant differences between the i.v. MSCs and i.c. MSCs groups in IL-6 levels. Neither treatment reduced infarction volume. However, cell death, measured as TUNEL+ cells was decreased with significant differences between control groups. BrdU+ cells were also significantly increased in the peri-infarct zone at 14 days. VEGF expression was significantly higher in the i.c. MSCs group than in the i.c. control group and blood vessel number was significantly higher in treated groups than control groups with significant differences in the peri-infarct zone at 14 days. We conclude that allogenic MSCs administration shows therapeutic efficacy in our acute ischemic stroke model. Both routes demonstrably improved neurological recovery and provided brain protection. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/21144885/Functional_recovery_after_hematic_administration_of_allogenic_mesenchymal_stem_cells_in_acute_ischemic_stroke_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(10)01545-9 DB - PRIME DP - Unbound Medicine ER -