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

Autor(es)

Araujo, Marta Rocha ; Kyrylenko, Sergiy ; Spejo, Aline Barroso ; Castro, Mateus Vidigal ; Ferreira Junior, Rui Seabra ; Barraviera, Benedito ; Rodrigues Oliveira, Alexandre Leite

• Tipo de documento: Artigo Científico
• Fonte: Experimental Neurology; v. 294, p. 45-57, AUG 2017.
• Citações Web of Science: 8

Resumo

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)

• Processo FAPESP: 14/06892-3 - Utilização de células tronco mesenquimais na interface do sistema nervoso central e periférico: reparo de lesões proximais
• Beneficiário: Alexandre Leite Rodrigues de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/20456-6 - Participação de moléculas do complexo principal de histocompatibilidade de classe I na reatividade astrocitária após transecção do nervo isquiático
• Beneficiário: Sérgio Luiz Oliveira Nunes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 13/22045-6 - Aplicação da bioengenharia em células tronco embrionárias humanas com superexpressão de FGF2 para estudar a sobrevivência dos motoneurônios em modelo animal de avulsão da raiz ventral
• Beneficiário: Sergiy Kyrylenko
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/23030-2 - Emprego de células tronco embrionárias humanas com superexpressão de FGF2 após avulsão de raízes ventrais medulares: neuroproteção e imunomodulação
• Beneficiário: Marta Rocha Araujo
• Modalidade de apoio: Bolsas no Brasil - Doutorado