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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Transgenic human embryonic stem cells overexpressing FGF2 stimulate neuroprotection following spinal cord ventral root avulsion

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Author(s):
Araujo, Marta Rocha ; Kyrylenko, Sergiy ; Spejo, Aline Barroso ; Castro, Mateus Vidigal ; Ferreira Junior, Rui Seabra ; Barraviera, Benedito ; Rodrigues Oliveira, Alexandre Leite
Total Authors: 7
Document type: Journal article
Source: Experimental Neurology; v. 294, p. 45-57, AUG 2017.
Web of Science Citations: 8
Abstract

Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESC/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity two weeks post lesion. Then, qRT-PCR was used to assess gene expression of beta 2-microglobulin (beta 2m), TNF alpha, IL6 and 110 in the spinal cord in vivo and FGF2 mRNA levels in hESC in vitro. The results indicate that hESC overexpressing FGF2 significantly rescued avulsed motoneurons, preserving synaptic covering and reducing astroglial reactivity. The cells were also shown to express BDNF and GDNF at the site of injury. Additionally, engraftment of hESC led to a significant reduction in mRNA levels of TNF alpha at the spinal cord ventral horn, indicating their immunomodulatory properties. Overall, the present data suggest that hESC overexpressing FGF2 are neuroprotective and can shift gene expression towards an anti-inflammatory environment. (C) 2017 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 14/06892-3 - Use of mesenchymal stem cells in the CNS/PNS interface: repair of proximal lesions
Grantee:Alexandre Leite Rodrigues de Oliveira
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 12/20456-6 - The involvement of the major histocompatibility complex class I molecules in the astrocytic reactivity after sciatic nerve transection
Grantee:Sérgio Luiz Oliveira Nunes
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 13/22045-6 - Application of bioengineered human embryonic stem cells overexpressing FGF2 to study motoneuron survival in animal model of ventral root avulsion
Grantee:Sergiy Kyrylenko
Support Opportunities: Regular Research Grants
FAPESP's process: 13/23030-2 - Application of human embryonic stem cells overexpressing FGF2 after ventral root avulsion: neuroprotection and immunomodulation
Grantee:Marta Rocha Araujo
Support Opportunities: Scholarships in Brazil - Doctorate