BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury

We investigated whether irradiated brain-derived neurotropic factor (BDNF)-overexpressing engineered human mesenchymal stem cells (BDNF-eMSCs) improve paracrine efficiency and, thus, the beneficial potency of naïve MSCs against severe hypoxic ischemic (HI) brain injury in newborn rats. Irradiated BD...

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Autores principales:	So Yoon Ahn, Dong Kyung Sung, Yun Sil Chang, Se In Sung, Young Eun Kim, Hyo-Jin Kim, Soon Min Lee, Won Soon Park
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hypoxia-ischemia brain cell transplantation stem cells mesenchymal stem cell transplantation infant Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/f2cfe3b3868a4634bc1168e8991aea54
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spelling	oai:doaj.org-article:f2cfe3b3868a4634bc1168e8991aea542021-11-11T16:52:21ZBDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury10.3390/ijms2221113951422-00671661-6596https://doaj.org/article/f2cfe3b3868a4634bc1168e8991aea542021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11395https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067We investigated whether irradiated brain-derived neurotropic factor (BDNF)-overexpressing engineered human mesenchymal stem cells (BDNF-eMSCs) improve paracrine efficiency and, thus, the beneficial potency of naïve MSCs against severe hypoxic ischemic (HI) brain injury in newborn rats. Irradiated BDNF-eMSCs hyper-secreted BDNF > 10 fold and were >5 fold more effective than naïve MSCs in attenuating the oxygen-glucose deprivation-induced increase in cytotoxicity, oxidative stress, and cell death in vitro. Only the irradiated BDNF-eMSCs, but not naïve MSCs, showed significant attenuating effects on severe neonatal HI-induced short-term brain injury scores, long-term progress of brain infarct, increased apoptotic cell death, astrogliosis and inflammatory responses, and impaired negative geotaxis and rotarod tests in vivo. Our data, showing better paracrine potency and the resultant better therapeutic efficacy of the irradiated BDNF-eMSCs, compared to naïve MSCs, suggest that MSCs transfected with the BDNF gene might represent a better, new therapeutic strategy against severe neonatal HI brain injury.So Yoon AhnDong Kyung SungYun Sil ChangSe In SungYoung Eun KimHyo-Jin KimSoon Min LeeWon Soon ParkMDPI AGarticlehypoxia-ischemiabraincell transplantationstem cellsmesenchymal stem cell transplantationinfantBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11395, p 11395 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypoxia-ischemia brain cell transplantation stem cells mesenchymal stem cell transplantation infant Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	hypoxia-ischemia brain cell transplantation stem cells mesenchymal stem cell transplantation infant Biology (General) QH301-705.5 Chemistry QD1-999 So Yoon Ahn Dong Kyung Sung Yun Sil Chang Se In Sung Young Eun Kim Hyo-Jin Kim Soon Min Lee Won Soon Park BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury
description	We investigated whether irradiated brain-derived neurotropic factor (BDNF)-overexpressing engineered human mesenchymal stem cells (BDNF-eMSCs) improve paracrine efficiency and, thus, the beneficial potency of naïve MSCs against severe hypoxic ischemic (HI) brain injury in newborn rats. Irradiated BDNF-eMSCs hyper-secreted BDNF > 10 fold and were >5 fold more effective than naïve MSCs in attenuating the oxygen-glucose deprivation-induced increase in cytotoxicity, oxidative stress, and cell death in vitro. Only the irradiated BDNF-eMSCs, but not naïve MSCs, showed significant attenuating effects on severe neonatal HI-induced short-term brain injury scores, long-term progress of brain infarct, increased apoptotic cell death, astrogliosis and inflammatory responses, and impaired negative geotaxis and rotarod tests in vivo. Our data, showing better paracrine potency and the resultant better therapeutic efficacy of the irradiated BDNF-eMSCs, compared to naïve MSCs, suggest that MSCs transfected with the BDNF gene might represent a better, new therapeutic strategy against severe neonatal HI brain injury.
format	article
author	So Yoon Ahn Dong Kyung Sung Yun Sil Chang Se In Sung Young Eun Kim Hyo-Jin Kim Soon Min Lee Won Soon Park
author_facet	So Yoon Ahn Dong Kyung Sung Yun Sil Chang Se In Sung Young Eun Kim Hyo-Jin Kim Soon Min Lee Won Soon Park
author_sort	So Yoon Ahn
title	BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury
title_short	BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury
title_full	BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury
title_fullStr	BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury
title_full_unstemmed	BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury
title_sort	bdnf-overexpressing engineered mesenchymal stem cells enhances their therapeutic efficacy against severe neonatal hypoxic ischemic brain injury
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f2cfe3b3868a4634bc1168e8991aea54
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BDNF-Overexpressing Engineered Mesenchymal Stem Cells Enhances Their Therapeutic Efficacy against Severe Neonatal Hypoxic Ischemic Brain Injury

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