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Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice

In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury (SCI) are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory mi...

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Autores principales: Ramalho, Bruna dos Santos, de Almeida, Fernanda Martins, Sales, Conrado Mendonça, de Lima, Silmara, Martinez, Ana Maria Blanco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022457/
https://www.ncbi.nlm.nih.gov/pubmed/29926832
http://dx.doi.org/10.4103/1673-5374.233448
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author Ramalho, Bruna dos Santos
de Almeida, Fernanda Martins
Sales, Conrado Mendonça
de Lima, Silmara
Martinez, Ana Maria Blanco
author_facet Ramalho, Bruna dos Santos
de Almeida, Fernanda Martins
Sales, Conrado Mendonça
de Lima, Silmara
Martinez, Ana Maria Blanco
author_sort Ramalho, Bruna dos Santos
collection PubMed
description In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury (SCI) are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory microenvironment. Assorted lineages of stem cells are considered a good treatment for SCI. This study investigated the effect of systemic transplantation of mesenchymal stem cells (MSCs) in a compressive SCI model. Here we present results of the intraperitoneal route, which has not been used previously for MSC administration after compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T(9) level, followed by spinal cord compression for 1 minute with a 30-g vascular clip. The animals were divided into five groups: sham (anesthesia and laminectomy but without compression injury induction), MSC i.p. (intraperitoneal injection of 8 × 10(5) MSCs in 500 µL of DMEM at 7 days after SCI), MSC i.v. (intravenous injection of 8 × 10(5) MSCs in 500 µL of DMEM at 7 days after SCI), DMEM i.p. (intraperitoneal injection of 500 µL of DMEM at 7 days after SCI), DMEM i.v. (intravenous injection of 500 µL of DMEM at 7 days after SCI). The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining. The number of preserved fibers was counted in semithin sections stained with toluidine blue and the presence of trophic factors was analyzed by immunohistochemistry. In addition, we analyzed the locomotor performance with Basso Mouse Scale and Global Mobility Test. Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups. Furthermore, the MSC groups had higher levels of trophic factors (brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and neurotrophin-4) in the spinal cord and improved locomotor performance. Our results indicate that injection of MSCs by either intraperitoneal or intravenous routes results in beneficial outcomes and can be elected as a choice for SCI treatment.
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spelling pubmed-60224572018-07-13 Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice Ramalho, Bruna dos Santos de Almeida, Fernanda Martins Sales, Conrado Mendonça de Lima, Silmara Martinez, Ana Maria Blanco Neural Regen Res Research Article In spite of advances in surgical care and rehabilitation, the consequences of spinal cord injury (SCI) are still challenging. Several experimental therapeutic strategies have been studied in the SCI field, and recent advances have led to the development of therapies that may act on the inhibitory microenvironment. Assorted lineages of stem cells are considered a good treatment for SCI. This study investigated the effect of systemic transplantation of mesenchymal stem cells (MSCs) in a compressive SCI model. Here we present results of the intraperitoneal route, which has not been used previously for MSC administration after compressive SCI. We used adult female C57BL/6 mice that underwent laminectomy at the T(9) level, followed by spinal cord compression for 1 minute with a 30-g vascular clip. The animals were divided into five groups: sham (anesthesia and laminectomy but without compression injury induction), MSC i.p. (intraperitoneal injection of 8 × 10(5) MSCs in 500 µL of DMEM at 7 days after SCI), MSC i.v. (intravenous injection of 8 × 10(5) MSCs in 500 µL of DMEM at 7 days after SCI), DMEM i.p. (intraperitoneal injection of 500 µL of DMEM at 7 days after SCI), DMEM i.v. (intravenous injection of 500 µL of DMEM at 7 days after SCI). The effects of MSCs transplantation in white matter sparing were analyzed by luxol fast blue staining. The number of preserved fibers was counted in semithin sections stained with toluidine blue and the presence of trophic factors was analyzed by immunohistochemistry. In addition, we analyzed the locomotor performance with Basso Mouse Scale and Global Mobility Test. Our results showed white matter preservation and a larger number of preserved fibers in the MSC groups than in the DMEM groups. Furthermore, the MSC groups had higher levels of trophic factors (brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and neurotrophin-4) in the spinal cord and improved locomotor performance. Our results indicate that injection of MSCs by either intraperitoneal or intravenous routes results in beneficial outcomes and can be elected as a choice for SCI treatment. Medknow Publications & Media Pvt Ltd 2018-06 /pmc/articles/PMC6022457/ /pubmed/29926832 http://dx.doi.org/10.4103/1673-5374.233448 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Ramalho, Bruna dos Santos
de Almeida, Fernanda Martins
Sales, Conrado Mendonça
de Lima, Silmara
Martinez, Ana Maria Blanco
Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice
title Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice
title_full Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice
title_fullStr Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice
title_full_unstemmed Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice
title_short Injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice
title_sort injection of bone marrow mesenchymal stem cells by intravenous or intraperitoneal routes is a viable alternative to spinal cord injury treatment in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022457/
https://www.ncbi.nlm.nih.gov/pubmed/29926832
http://dx.doi.org/10.4103/1673-5374.233448
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