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Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) occurs when an infant’s brain has not received adequate oxygen and blood supply, resulting in ischemic and hypoxic damage. Currently, supportive care and hypothermia therapy have been the standard treatment for HIE. However, there are still over 20%...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924590/ https://www.ncbi.nlm.nih.gov/pubmed/35308119 http://dx.doi.org/10.3389/fncel.2022.823320 |
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author | Lyu, Hao Sun, Dong Ming Ng, Chi Ping Cheng, Wendy S. Chen, Jun Fan He, Yu Zhong Lam, Sin Yu Zheng, Zhi Yuan Huang, Guo Dong Wang, Chi Chiu Young, Wise Poon, Wai Sang |
author_facet | Lyu, Hao Sun, Dong Ming Ng, Chi Ping Cheng, Wendy S. Chen, Jun Fan He, Yu Zhong Lam, Sin Yu Zheng, Zhi Yuan Huang, Guo Dong Wang, Chi Chiu Young, Wise Poon, Wai Sang |
author_sort | Lyu, Hao |
collection | PubMed |
description | BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) occurs when an infant’s brain has not received adequate oxygen and blood supply, resulting in ischemic and hypoxic damage. Currently, supportive care and hypothermia therapy have been the standard treatment for HIE. However, there are still over 20% of treated infants died and 19–30% survived with significant disability. HIE animal model was first established by Rice et al., involving the ligation of one common carotid artery followed by hypoxia. In this study, we investigated human umbilical cord blood (HUCB) and its two components mononuclear cell (MNC) and red cell fraction (RCF) in both short and long term study using a modified HIE rat model. METHODS: In this modified HIE model, both common carotid arteries were occluded, breathing 8% oxygen in a hypoxic chamber for 60-min, followed by the release of the common carotid arteries ligature, mimicking reperfusion injury. For cell therapeutic study, cells were intravenously injected to HIE rat pups, and both behavioral and histological changes were assessed at selected time points. RESULT: Statistically significant behavioral improvements were demonstrated on Day 7 and 1 month between saline treated HIE rats and UCB/MNC treated rats. However, at 3 months, the therapeutic improvements were only showed between saline treated HIE animals and MNC treated HIE rats. For histological analysis 1 month after cell injection, the number of functional neurons were statistically increased between saline treated HIE and UCB/MNC/RCF treated HIE rats. At 3 months, the significant increase in functional neurons was only present in MNC treated HIE rats. CONCLUSION: We have used a bilateral temporary occlusion of 60 min, a moderately brain damaged model, for cell therapeutic studies. HUCB mononuclear cell (MNC) therapy showed benefits in neonatal HIE rats in both short and long term behavioral and histological assessments. |
format | Online Article Text |
id | pubmed-8924590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89245902022-03-17 Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia Lyu, Hao Sun, Dong Ming Ng, Chi Ping Cheng, Wendy S. Chen, Jun Fan He, Yu Zhong Lam, Sin Yu Zheng, Zhi Yuan Huang, Guo Dong Wang, Chi Chiu Young, Wise Poon, Wai Sang Front Cell Neurosci Neuroscience BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) occurs when an infant’s brain has not received adequate oxygen and blood supply, resulting in ischemic and hypoxic damage. Currently, supportive care and hypothermia therapy have been the standard treatment for HIE. However, there are still over 20% of treated infants died and 19–30% survived with significant disability. HIE animal model was first established by Rice et al., involving the ligation of one common carotid artery followed by hypoxia. In this study, we investigated human umbilical cord blood (HUCB) and its two components mononuclear cell (MNC) and red cell fraction (RCF) in both short and long term study using a modified HIE rat model. METHODS: In this modified HIE model, both common carotid arteries were occluded, breathing 8% oxygen in a hypoxic chamber for 60-min, followed by the release of the common carotid arteries ligature, mimicking reperfusion injury. For cell therapeutic study, cells were intravenously injected to HIE rat pups, and both behavioral and histological changes were assessed at selected time points. RESULT: Statistically significant behavioral improvements were demonstrated on Day 7 and 1 month between saline treated HIE rats and UCB/MNC treated rats. However, at 3 months, the therapeutic improvements were only showed between saline treated HIE animals and MNC treated HIE rats. For histological analysis 1 month after cell injection, the number of functional neurons were statistically increased between saline treated HIE and UCB/MNC/RCF treated HIE rats. At 3 months, the significant increase in functional neurons was only present in MNC treated HIE rats. CONCLUSION: We have used a bilateral temporary occlusion of 60 min, a moderately brain damaged model, for cell therapeutic studies. HUCB mononuclear cell (MNC) therapy showed benefits in neonatal HIE rats in both short and long term behavioral and histological assessments. Frontiers Media S.A. 2022-03-02 /pmc/articles/PMC8924590/ /pubmed/35308119 http://dx.doi.org/10.3389/fncel.2022.823320 Text en Copyright © 2022 Lyu, Sun, Ng, Cheng, Chen, He, Lam, Zheng, Huang, Wang, Young and Poon. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Lyu, Hao Sun, Dong Ming Ng, Chi Ping Cheng, Wendy S. Chen, Jun Fan He, Yu Zhong Lam, Sin Yu Zheng, Zhi Yuan Huang, Guo Dong Wang, Chi Chiu Young, Wise Poon, Wai Sang Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia |
title | Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia |
title_full | Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia |
title_fullStr | Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia |
title_full_unstemmed | Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia |
title_short | Umbilical Cord Blood Mononuclear Cell Treatment for Neonatal Rats With Hypoxic Ischemia |
title_sort | umbilical cord blood mononuclear cell treatment for neonatal rats with hypoxic ischemia |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924590/ https://www.ncbi.nlm.nih.gov/pubmed/35308119 http://dx.doi.org/10.3389/fncel.2022.823320 |
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