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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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Official URL: http://dx.doi.org/10.1089/scd.2019.0176

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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
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:
DateEvent
24 April 2020Published
9 April 2020Available
11 March 2020Accepted
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:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDBrazil. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Ciência e Tecnologiahttp://viaf.org/viaf/129365128
402319/2013-3Conselho nacional de desenvolvimento cientifico e tecnologicohttp://viaf.org/viaf/154202039
88887.136364/2017-00CAPES (Organization : Brazil)http://viaf.org/viaf/219588473
PROBITEC 2262/2012 - 23038.004161/2018-88CAPES (Organization : Brazil)http://viaf.org/viaf/219588473
Edital 19/2016Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeirohttp://viaf.org/viaf/121741474

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