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Intravenous human umbilical cord-derived mesenchymal stromal cell administration in models of moderate and severe intracerebral hemorrhage
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Mello, Tanira Giara, Rosado-de-Castro, Paulo Henrique, Campos, Raquel Maria Pereira, Vasques, Juliana Ferreira, Rangel Junior, William Simões, Mattos, Raphael Santos de Almeida Rezende, Puig-Pijuan, Teresa, Foerster, Bernd Uwe, Gutfilen, Bianca, Souza, Sergio Augusto Lopes, Boltze, Johannes, Paiva, Fernando Fernandes, Mendez-Otero, Rosalia and Pimentel-Coelho, Pedro Moreno (2020) Intravenous human umbilical cord-derived mesenchymal stromal cell administration in models of moderate and severe intracerebral hemorrhage. Stem Cells and Development, 29 (9). pp. 586-598. doi:10.1089/scd.2019.0176
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WRAP-intravenous-human-umbilical-cord-derived-medenchymal-stomal-Boltz-2020.pdf - Accepted Version - Requires a PDF viewer. Download (1814Kb) | Preview |
Official URL: http://dx.doi.org/10.1089/scd.2019.0176
Abstract
Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggests mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared to other disorders such as ischemic stroke. Herein, we employed a model of collagenase-induced ICH in young adult rats to investigate the potential therapeutic effects of an intravenous injection of human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs). Two doses of collagenase were used to cause moderate or severe hemorrhages. Magnetic resonance imaging showed that animals treated with hUC-MSCs after moderate ICH had smaller residual hematoma volumes than vehicle-treated rats, whereas the cell therapy failed to decrease the hematoma volume in animals with a severe ICH. Functional assessments (rotarod and elevated body swing tests) were performed for up to 21 days after ICH. Enduring neurological impairments were seen only in animals subjected to severe ICH, but the cell therapy did not induce statistically significant improvements in the functional recovery. The biodistribution of Technetium-99m-labeled hUC-MSCs was also evaluated, showing that most cells were found in organs such as the spleen and lungs 24 h after transplantation. Nevertheless, it was possible to detect a weak signal in the brain, which was higher in the ipsilateral hemisphere of rats subjected to a severe ICH. These data indicate that hUC-MSCs have moderately beneficial effects in cases of less severe brain hemorrhages in rats by decreasing the residual hematoma volume, and that optimization of the therapy is still necessary.
| Item Type: | Journal Article | ||||||||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | ||||||||||||||||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Cellular therapy, Brain -- Hemorrhage, Mesenchymal stem cells -- Therapeutic use, Cerebrovascular disease -- Treatment | ||||||||||||||||||
| Journal or Publication Title: | Stem Cells and Development | ||||||||||||||||||
| Publisher: | Mary Ann Liebert | ||||||||||||||||||
| ISSN: | 1547-3287 | ||||||||||||||||||
| Official Date: | 24 April 2020 | ||||||||||||||||||
| Dates: |
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| Volume: | 29 | ||||||||||||||||||
| Number: | 9 | ||||||||||||||||||
| Page Range: | pp. 586-598 | ||||||||||||||||||
| DOI: | 10.1089/scd.2019.0176 | ||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||
| Publisher Statement: | Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/scd.2019.0176 | ||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||
| RIOXX Funder/Project Grant: |
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