Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone
Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-06-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fnagi.2014.00130/full |
| _version_ | 1828743043551854592 |
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| author | Adrian Tudor Balseanu Ana-Maria Buga Ana-Maria Buga Bogdan Catalin Daniel-Christoph Wagner Johannes Boltze Johannes Boltze Johannes Boltze Ana-Maria Zagrean Klaus Reymann Wolf Schaebitz Aurel Popa-Wagner Aurel Popa-Wagner |
| author_facet | Adrian Tudor Balseanu Ana-Maria Buga Ana-Maria Buga Bogdan Catalin Daniel-Christoph Wagner Johannes Boltze Johannes Boltze Johannes Boltze Ana-Maria Zagrean Klaus Reymann Wolf Schaebitz Aurel Popa-Wagner Aurel Popa-Wagner |
| author_sort | Adrian Tudor Balseanu |
| collection | DOAJ |
| description | Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the stem cell mobilizer granulocyte colony-stimulating factor (G-CSF). We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs) in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 μg/kg) or in combination with a single dose (106 cells) of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min) of the middle cerebral artery. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration.” However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time. |
| first_indexed | 2024-04-13T01:29:34Z |
| format | Article |
| id | doaj.art-2a927c0076294b40a53bab10cab47f7d |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T01:29:34Z |
| publishDate | 2014-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-2a927c0076294b40a53bab10cab47f7d2022-12-22T03:08:32ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652014-06-01610.3389/fnagi.2014.0013093751Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF AloneAdrian Tudor Balseanu0Ana-Maria Buga1Ana-Maria Buga2Bogdan Catalin3Daniel-Christoph Wagner4Johannes Boltze5Johannes Boltze6Johannes Boltze7Ana-Maria Zagrean8Klaus Reymann9Wolf Schaebitz10Aurel Popa-Wagner11Aurel Popa-Wagner12Center of Clinical and Experimental Medicine, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaCenter of Clinical and Experimental Medicine, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaDepartment of Psychiatry, University Medicine of Rostock, Rostock, GermanyCenter of Clinical and Experimental Medicine, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaFraunhofer Institute for Cell Therapy and Immunology, Leipzig, GermanyFraunhofer Institute for Cell Therapy and Immunology, Leipzig, GermanyTranslational Center for Regenerative Medicine, University of Leipzig, Leipzig, GermanyStroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USACarol Davila University of Medicine and Pharmacy, Bucharest, RomaniaGerman Center for Neurodegenerative Diseases (DZNE) Magdeburg in collobaration with Leibniz Institute for Neurobiology, Magdeburg, GermanyEvangelisches Krankenhaus Bielefeld gGmbH Akademisches Lehrkrankenhaus der Universität Münster, Münster, GermanyCenter of Clinical and Experimental Medicine, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaDepartment of Psychiatry, University Medicine of Rostock, Rostock, GermanyAttractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the stem cell mobilizer granulocyte colony-stimulating factor (G-CSF). We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs) in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 μg/kg) or in combination with a single dose (106 cells) of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min) of the middle cerebral artery. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the “islet of regeneration.” However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time.http://journal.frontiersin.org/article/10.3389/fnagi.2014.00130/fullagingstrokecell therapyG-CSFtranslational medicineBM MSC |
| spellingShingle | Adrian Tudor Balseanu Ana-Maria Buga Ana-Maria Buga Bogdan Catalin Daniel-Christoph Wagner Johannes Boltze Johannes Boltze Johannes Boltze Ana-Maria Zagrean Klaus Reymann Wolf Schaebitz Aurel Popa-Wagner Aurel Popa-Wagner Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone Frontiers in Aging Neuroscience aging stroke cell therapy G-CSF translational medicine BM MSC |
| title | Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone |
| title_full | Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone |
| title_fullStr | Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone |
| title_full_unstemmed | Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone |
| title_short | Multimodal Approaches for Regenerative Stroke Therapies: Combination of Granulocyte Colony-Stimulating Factor with Bone Marrow Mesenchymal Stem Cells is Not Superior to G-CSF Alone |
| title_sort | multimodal approaches for regenerative stroke therapies combination of granulocyte colony stimulating factor with bone marrow mesenchymal stem cells is not superior to g csf alone |
| topic | aging stroke cell therapy G-CSF translational medicine BM MSC |
| url | http://journal.frontiersin.org/article/10.3389/fnagi.2014.00130/full |
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