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Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats

Recently, we showed that intracerebroventricular (IC) transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuates posthemorrhagic hydrocephalus (PHH) and brain damage after severe IVH in newborn rats. This study was performed to determine the op...

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Autores principales: Ahn, So Yoon, Chang, Yun Sil, Sung, Dong Kyung, Sung, Se In, Yoo, Hye Soo, Im, Geun Ho, Choi, Soo Jin, Park, Won Soon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514759/
https://www.ncbi.nlm.nih.gov/pubmed/26208299
http://dx.doi.org/10.1371/journal.pone.0132919
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author Ahn, So Yoon
Chang, Yun Sil
Sung, Dong Kyung
Sung, Se In
Yoo, Hye Soo
Im, Geun Ho
Choi, Soo Jin
Park, Won Soon
author_facet Ahn, So Yoon
Chang, Yun Sil
Sung, Dong Kyung
Sung, Se In
Yoo, Hye Soo
Im, Geun Ho
Choi, Soo Jin
Park, Won Soon
author_sort Ahn, So Yoon
collection PubMed
description Recently, we showed that intracerebroventricular (IC) transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuates posthemorrhagic hydrocephalus (PHH) and brain damage after severe IVH in newborn rats. This study was performed to determine the optimal route for transplanting MSCs for severe IVH by comparing IC transplantation, intravenous (IV) transplantation, and IV transplantation plus mannitol infusion. Severe IVH was induced by injecting 100 uL of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4). After confirming severe IVH with brain magnetic resonance imaging (MRI) at P5, human UCB-derived MSCs were transplanted at P6 by an IC route (1×10(5)), an IV route (5×10(5)), or an IV route with mannitol infused. Follow-up brain MRIs and rotarod tests were performed. At P32, brain tissue samples were obtained for biochemical and histological analyses. Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion. Despite the superior delivery efficacy with IC than with the IV route, both IC and IV transplantation of MSCs had equal therapeutic efficacy in protecting against severe IVH. These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs.
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spelling pubmed-45147592015-07-29 Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats Ahn, So Yoon Chang, Yun Sil Sung, Dong Kyung Sung, Se In Yoo, Hye Soo Im, Geun Ho Choi, Soo Jin Park, Won Soon PLoS One Research Article Recently, we showed that intracerebroventricular (IC) transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuates posthemorrhagic hydrocephalus (PHH) and brain damage after severe IVH in newborn rats. This study was performed to determine the optimal route for transplanting MSCs for severe IVH by comparing IC transplantation, intravenous (IV) transplantation, and IV transplantation plus mannitol infusion. Severe IVH was induced by injecting 100 uL of blood into each ventricle of Sprague-Dawley rats on postnatal day 4 (P4). After confirming severe IVH with brain magnetic resonance imaging (MRI) at P5, human UCB-derived MSCs were transplanted at P6 by an IC route (1×10(5)), an IV route (5×10(5)), or an IV route with mannitol infused. Follow-up brain MRIs and rotarod tests were performed. At P32, brain tissue samples were obtained for biochemical and histological analyses. Although more MSCs localized to the brain after IC than after IV delivery, both methods were equally effective in preventing PHH; attenuating impaired rotarod test; increasing the number of TUNEL-positive cells, inflammatory cytokines, and astrogliosis; and reducing corpus callosal thickness and myelin basic protein expression after severe IVH regardless of mannitol co-infusion. Despite the superior delivery efficacy with IC than with the IV route, both IC and IV transplantation of MSCs had equal therapeutic efficacy in protecting against severe IVH. These findings suggest that the less invasive IV route might be a good alternative for clinically unstable, very preterm infants that cannot tolerate a more invasive IC delivery of MSCs. Public Library of Science 2015-07-24 /pmc/articles/PMC4514759/ /pubmed/26208299 http://dx.doi.org/10.1371/journal.pone.0132919 Text en © 2015 Ahn et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ahn, So Yoon
Chang, Yun Sil
Sung, Dong Kyung
Sung, Se In
Yoo, Hye Soo
Im, Geun Ho
Choi, Soo Jin
Park, Won Soon
Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats
title Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats
title_full Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats
title_fullStr Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats
title_full_unstemmed Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats
title_short Optimal Route for Mesenchymal Stem Cells Transplantation after Severe Intraventricular Hemorrhage in Newborn Rats
title_sort optimal route for mesenchymal stem cells transplantation after severe intraventricular hemorrhage in newborn rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514759/
https://www.ncbi.nlm.nih.gov/pubmed/26208299
http://dx.doi.org/10.1371/journal.pone.0132919
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