Breaking the Blood–Brain Barrier with Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain
Blood–brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2016-08-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368916X690971 |
| _version_ | 1811328089035112448 |
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| author | Naoki Tajiri Jea Young Lee Sandra Acosta Paul R. Sanberg Cesar V. Borlongan |
| author_facet | Naoki Tajiri Jea Young Lee Sandra Acosta Paul R. Sanberg Cesar V. Borlongan |
| author_sort | Naoki Tajiri |
| collection | DOAJ |
| description | Blood–brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague–Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke. |
| first_indexed | 2024-04-13T15:18:57Z |
| format | Article |
| id | doaj.art-7b539b316d98454e95c5f040d589fdff |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-04-13T15:18:57Z |
| publishDate | 2016-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-7b539b316d98454e95c5f040d589fdff2022-12-22T02:41:44ZengSAGE PublishingCell Transplantation0963-68971555-38922016-08-012510.3727/096368916X690971Breaking the Blood–Brain Barrier with Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke BrainNaoki Tajiri0Jea Young Lee1Sandra Acosta2Paul R. Sanberg3Cesar V. Borlongan4Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USADepartment of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USADepartment of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USADepartment of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USADepartment of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USABlood–brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague–Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.https://doi.org/10.3727/096368916X690971 |
| spellingShingle | Naoki Tajiri Jea Young Lee Sandra Acosta Paul R. Sanberg Cesar V. Borlongan Breaking the Blood–Brain Barrier with Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain Cell Transplantation |
| title | Breaking the Blood–Brain Barrier with Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain |
| title_full | Breaking the Blood–Brain Barrier with Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain |
| title_fullStr | Breaking the Blood–Brain Barrier with Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain |
| title_full_unstemmed | Breaking the Blood–Brain Barrier with Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain |
| title_short | Breaking the Blood–Brain Barrier with Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain |
| title_sort | breaking the blood brain barrier with mannitol to aid stem cell therapeutics in the chronic stroke brain |
| url | https://doi.org/10.3727/096368916X690971 |
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