Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage
We recently showed that intraventricular transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuated posthemorrhagic hydrocephalus (PHH) and brain injury after severe intraventricular hemorrhage (IVH) in newborn rat pups. The purpose of this stu...
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doaj-95829332598e45efbcf0d37b1b69b7cd2020-11-25T03:09:24ZengSAGE PublishingCell Transplantation0963-68971555-38922016-06-012510.3727/096368915X689640Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular HemorrhageWon Soon Park0Se In Sung1So Yoon Ahn2Dong Kyung Sung3Geun Ho Im4Hye Soo Yoo5Soo Jin Choi6Yun Sil Chang M.D., Ph.D.7Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaSamsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, KoreaSamsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, KoreaDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaBiomedical Research Institute, MEDIPOST Co., Ltd., Seoul, KoreaDepartment of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, KoreaWe recently showed that intraventricular transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuated posthemorrhagic hydrocephalus (PHH) and brain injury after severe intraventricular hemorrhage (IVH) in newborn rat pups. The purpose of this study was to optimize the timing of MSC transplantation for severe IVH. Severe IVH was induced by injecting 100 μl of blood into each ventricle of Sprague–Dawley rats on postnatal day 4 (P4). Human UCB-derived MSCs (1 × 10 5 cells in 10 μl of normal saline) were transplanted intraventricularly under stereotaxic guidance either early at P6 or late at P11. Serial brain MRIs and behavioral function tests, such as negative geotaxis and rotarod tests, were performed. At P32, brain tissue samples were obtained for histological and biochemical analyses. Intracerebroventricular transplantation of MSCs significantly attenuated the development of PHH, behavioral impairment, increased apoptosis and astrogliosis, reduced corpus callosum thickness and brain myelination, and upregulated inflammatory cytokines including interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) at P6 but not at P11 after induction of severe IVH. Intracerebroventricular transplantation of human UCB-derived MSCs attenuated PHH and brain injury after severe IVH in newborn rats in a time-dependent manner. Significant neuroprotection was only demonstrated when administered early at 2 days after induction but not late at 7 days after induction of severe IVH.https://doi.org/10.3727/096368915X689640 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Won Soon Park Se In Sung So Yoon Ahn Dong Kyung Sung Geun Ho Im Hye Soo Yoo Soo Jin Choi Yun Sil Chang M.D., Ph.D. |
spellingShingle |
Won Soon Park Se In Sung So Yoon Ahn Dong Kyung Sung Geun Ho Im Hye Soo Yoo Soo Jin Choi Yun Sil Chang M.D., Ph.D. Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage Cell Transplantation |
author_facet |
Won Soon Park Se In Sung So Yoon Ahn Dong Kyung Sung Geun Ho Im Hye Soo Yoo Soo Jin Choi Yun Sil Chang M.D., Ph.D. |
author_sort |
Won Soon Park |
title |
Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage |
title_short |
Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage |
title_full |
Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage |
title_fullStr |
Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage |
title_full_unstemmed |
Optimal Timing of Mesenchymal Stem Cell Therapy for Neonatal Intraventricular Hemorrhage |
title_sort |
optimal timing of mesenchymal stem cell therapy for neonatal intraventricular hemorrhage |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2016-06-01 |
description |
We recently showed that intraventricular transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly attenuated posthemorrhagic hydrocephalus (PHH) and brain injury after severe intraventricular hemorrhage (IVH) in newborn rat pups. The purpose of this study was to optimize the timing of MSC transplantation for severe IVH. Severe IVH was induced by injecting 100 μl of blood into each ventricle of Sprague–Dawley rats on postnatal day 4 (P4). Human UCB-derived MSCs (1 × 10 5 cells in 10 μl of normal saline) were transplanted intraventricularly under stereotaxic guidance either early at P6 or late at P11. Serial brain MRIs and behavioral function tests, such as negative geotaxis and rotarod tests, were performed. At P32, brain tissue samples were obtained for histological and biochemical analyses. Intracerebroventricular transplantation of MSCs significantly attenuated the development of PHH, behavioral impairment, increased apoptosis and astrogliosis, reduced corpus callosum thickness and brain myelination, and upregulated inflammatory cytokines including interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) at P6 but not at P11 after induction of severe IVH. Intracerebroventricular transplantation of human UCB-derived MSCs attenuated PHH and brain injury after severe IVH in newborn rats in a time-dependent manner. Significant neuroprotection was only demonstrated when administered early at 2 days after induction but not late at 7 days after induction of severe IVH. |
url |
https://doi.org/10.3727/096368915X689640 |
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