Cargando…

Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation

Several studies have reported that human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) restore neurological damage in vivo through their secretion of paracrine factors. We previously found that UC-MSCs attenuate brain injury by secreting neurotrophic factors, such as brain-derived neuro...

Descripción completa

Detalles Bibliográficos
Autores principales: Mukai, Takeo, Tojo, Arinobu, Nagamura-Inoue, Tokiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013549/
https://www.ncbi.nlm.nih.gov/pubmed/29963009
http://dx.doi.org/10.3389/fneur.2018.00466
_version_ 1783334036699086848
author Mukai, Takeo
Tojo, Arinobu
Nagamura-Inoue, Tokiko
author_facet Mukai, Takeo
Tojo, Arinobu
Nagamura-Inoue, Tokiko
author_sort Mukai, Takeo
collection PubMed
description Several studies have reported that human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) restore neurological damage in vivo through their secretion of paracrine factors. We previously found that UC-MSCs attenuate brain injury by secreting neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and hepatocyte growth factor (HGF). However, how these factors contribute to neuroprotection remains unknown. In this study, we aimed to investigate to what extent UC-MSC-derived HGF and BDNF contribute to neuroprotection using a Transwell co-culture system of neonatal cortical neurons damaged by oxygen-glucose deprivation. The influence of HGF and BDNF were determined by investigating neurons in both the presence and absence of UC-MSCs as these cells consistently secrete both factors and can be blocked by neutralizing antibodies. In the co-culture, UC-MSCs significantly improved neuronal injury, as indicated by an increase in immature neuron number, neurite outgrowth, and cell proliferation. Co-culture of damaged neurons with UC-MSCs also exhibited a reduction in the number of neurons displaying signs of apoptosis/necrosis. The neuroprotective actions of UC-MSCs were partially reverted by neutralizing antibodies. Together, our findings reveal that UC-MSC-secreted HGF and BDNF have neuroprotective effects on damaged neurons. Further studies should address the existence of other potential neurotrophic paracrine factors.
format Online
Article
Text
id pubmed-6013549
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-60135492018-06-29 Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation Mukai, Takeo Tojo, Arinobu Nagamura-Inoue, Tokiko Front Neurol Neurology Several studies have reported that human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) restore neurological damage in vivo through their secretion of paracrine factors. We previously found that UC-MSCs attenuate brain injury by secreting neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and hepatocyte growth factor (HGF). However, how these factors contribute to neuroprotection remains unknown. In this study, we aimed to investigate to what extent UC-MSC-derived HGF and BDNF contribute to neuroprotection using a Transwell co-culture system of neonatal cortical neurons damaged by oxygen-glucose deprivation. The influence of HGF and BDNF were determined by investigating neurons in both the presence and absence of UC-MSCs as these cells consistently secrete both factors and can be blocked by neutralizing antibodies. In the co-culture, UC-MSCs significantly improved neuronal injury, as indicated by an increase in immature neuron number, neurite outgrowth, and cell proliferation. Co-culture of damaged neurons with UC-MSCs also exhibited a reduction in the number of neurons displaying signs of apoptosis/necrosis. The neuroprotective actions of UC-MSCs were partially reverted by neutralizing antibodies. Together, our findings reveal that UC-MSC-secreted HGF and BDNF have neuroprotective effects on damaged neurons. Further studies should address the existence of other potential neurotrophic paracrine factors. Frontiers Media S.A. 2018-06-15 /pmc/articles/PMC6013549/ /pubmed/29963009 http://dx.doi.org/10.3389/fneur.2018.00466 Text en Copyright © 2018 Mukai, Tojo and Nagamura-Inoue. http://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 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 Neurology
Mukai, Takeo
Tojo, Arinobu
Nagamura-Inoue, Tokiko
Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation
title Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation
title_full Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation
title_fullStr Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation
title_full_unstemmed Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation
title_short Umbilical Cord-Derived Mesenchymal Stromal Cells Contribute to Neuroprotection in Neonatal Cortical Neurons Damaged by Oxygen-Glucose Deprivation
title_sort umbilical cord-derived mesenchymal stromal cells contribute to neuroprotection in neonatal cortical neurons damaged by oxygen-glucose deprivation
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013549/
https://www.ncbi.nlm.nih.gov/pubmed/29963009
http://dx.doi.org/10.3389/fneur.2018.00466
work_keys_str_mv AT mukaitakeo umbilicalcordderivedmesenchymalstromalcellscontributetoneuroprotectioninneonatalcorticalneuronsdamagedbyoxygenglucosedeprivation
AT tojoarinobu umbilicalcordderivedmesenchymalstromalcellscontributetoneuroprotectioninneonatalcorticalneuronsdamagedbyoxygenglucosedeprivation
AT nagamurainouetokiko umbilicalcordderivedmesenchymalstromalcellscontributetoneuroprotectioninneonatalcorticalneuronsdamagedbyoxygenglucosedeprivation