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Prostaglandin EP2 Receptors Mediate Mesenchymal Stromal Cell-Neuroprotective Effects on Dopaminergic Neurons

Parga, Juan Andrés ; García-Garrote, María LU orcid ; Martínez, Salvador ; Raya, Ángel ; Labandeira-García, José Luis and Rodríguez-Pallares, Jannette (2018) In Molecular Neurobiology 55(6). p.4763-4776
Abstract

Mesenchymal stromal cells (MSCs) have been shown to have useful properties for cell therapy and have been proposed for treatment of neurodegenerative diseases, including Parkinson’s disease. However, the mechanisms involved in recovering dopaminergic neurons are not clear. The present study aims to evaluate the pathways and molecules involved in the neuroprotective effect of MSCs. We analyzed the viability of dopaminergic cells from different sources in response to conditioned medium derived from bone marrow MSC (MSC-CM). MSC-CM increased the viability of dopaminergic cells of rat and human origins, having both neuroprotective and neurorescue activities against effects of dopaminergic neurotoxin 6-hydroxydopamine. We found that lipid... (More)

Mesenchymal stromal cells (MSCs) have been shown to have useful properties for cell therapy and have been proposed for treatment of neurodegenerative diseases, including Parkinson’s disease. However, the mechanisms involved in recovering dopaminergic neurons are not clear. The present study aims to evaluate the pathways and molecules involved in the neuroprotective effect of MSCs. We analyzed the viability of dopaminergic cells from different sources in response to conditioned medium derived from bone marrow MSC (MSC-CM). MSC-CM increased the viability of dopaminergic cells of rat and human origins, having both neuroprotective and neurorescue activities against effects of dopaminergic neurotoxin 6-hydroxydopamine. We found that lipid removal, inhibition of the prostaglandin E2 receptor 2 (EP2), and its signaling pathway were able to block the effects of MSC-CM on a pure population of dopaminergic neurons. Moreover, in primary mesencephalic cultures and hiPSC-derived neurons, inhibition of EP2 signaling caused a reduction in the number of dopaminergic neurons obtained in culture. Taken together, our results demonstrate for the first time the involvement of prostaglandin signaling from MSC in dopaminergic neuron survival through EP2 receptors, and suggest new approaches for treatment of Parkinson’s disease.

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author
; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Dopaminergic neurons, Mesenchymal stromal cells, Neuroprotection, Parkinson’s disease, Prostaglandin
in
Molecular Neurobiology
volume
55
issue
6
pages
4763 - 4776
publisher
Humana Press
external identifiers
  • scopus:85024488304
  • pmid:28717970
ISSN
0893-7648
DOI
10.1007/s12035-017-0681-5
language
English
LU publication?
no
additional info
Publisher Copyright: © 2017, Springer Science+Business Media, LLC.
id
3a2ce612-364a-4453-9ae4-e6855b70dcb9
date added to LUP
2025-01-24 11:51:09
date last changed
2025-03-21 16:49:12
@article{3a2ce612-364a-4453-9ae4-e6855b70dcb9,
  abstract     = {{<p>Mesenchymal stromal cells (MSCs) have been shown to have useful properties for cell therapy and have been proposed for treatment of neurodegenerative diseases, including Parkinson’s disease. However, the mechanisms involved in recovering dopaminergic neurons are not clear. The present study aims to evaluate the pathways and molecules involved in the neuroprotective effect of MSCs. We analyzed the viability of dopaminergic cells from different sources in response to conditioned medium derived from bone marrow MSC (MSC-CM). MSC-CM increased the viability of dopaminergic cells of rat and human origins, having both neuroprotective and neurorescue activities against effects of dopaminergic neurotoxin 6-hydroxydopamine. We found that lipid removal, inhibition of the prostaglandin E2 receptor 2 (EP2), and its signaling pathway were able to block the effects of MSC-CM on a pure population of dopaminergic neurons. Moreover, in primary mesencephalic cultures and hiPSC-derived neurons, inhibition of EP2 signaling caused a reduction in the number of dopaminergic neurons obtained in culture. Taken together, our results demonstrate for the first time the involvement of prostaglandin signaling from MSC in dopaminergic neuron survival through EP2 receptors, and suggest new approaches for treatment of Parkinson’s disease.</p>}},
  author       = {{Parga, Juan Andrés and García-Garrote, María and Martínez, Salvador and Raya, Ángel and Labandeira-García, José Luis and Rodríguez-Pallares, Jannette}},
  issn         = {{0893-7648}},
  keywords     = {{Dopaminergic neurons; Mesenchymal stromal cells; Neuroprotection; Parkinson’s disease; Prostaglandin}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{4763--4776}},
  publisher    = {{Humana Press}},
  series       = {{Molecular Neurobiology}},
  title        = {{Prostaglandin EP2 Receptors Mediate Mesenchymal Stromal Cell-Neuroprotective Effects on Dopaminergic Neurons}},
  url          = {{http://dx.doi.org/10.1007/s12035-017-0681-5}},
  doi          = {{10.1007/s12035-017-0681-5}},
  volume       = {{55}},
  year         = {{2018}},
}