Mesenchymal stem cells promote augmented response of endogenous neural stem cells in spinal cord injury of rats

Abstract

Traumatic spinal cord injury results in severe neurological deficits, mostly irreversible. The cell therapy represents a strategy for treatment particularly with the use of stem cells with satisfactory results in several experimental models. The aim of the study was to compare the treatment of spinal cord injury (SCI) with and without mesenchymal stem cells (MSC), to investigate whether MSCs migrate and/or remain at the site of injury, and to analyze the effects of MSCs on inflammation, astrocytic reactivity and activation of endogenous stem cells. Three hours after SCI, animals received bone marrow-derived MSCs (1×10 7 in 1mL PBS, IV). Animals were euthanized 24 hours, 7 and 21 days post-injury. The MSC were not present in the site of the lesion and the immunofluorescent evaluation showed significant attenuation of inflammatory response with reduction in macrophages labeled with anti-CD68 antibody (ED1), decreased immunoreactivity of astrocytes (GFAP+) and greater activation of endogenous stem cells (nestin+) in the treated groups. Therefore, cell transplantation have a positive effect on recovery from traumatic spinal cord injury possibly due to the potential of MSCs to attenuate the immune response. Key words: Cellular therapy. Neurosurgery. Stem cell. ResumoA lesão medular resulta em déficits neurológicos graves, a maioria irreversíveis. A terapia celular representa uma estratégia para o tratamento, especialmente com a utilização de células-tronco, com resultados satisfatórios em vários modelos experimentais. O objetivo do estudo foi comparar o tratamento de lesões da medula espinal (SCI), com e sem o uso de células-tronco mesenquimais (MSC), para investigar se as MSCs migram e/ou permanecem no local de lesão, e para analisar os efeitos de MSCs sobre a inflamação, reatividade astrocitária e ativação das células-tronco endógenas. Três horas depois da SCI, os animais receberam as MSC derivadas da medula óssea (1 × 10 7 em 1 mL de PBS, IV). Os animais foram sacrificados 24 horas, 7 e 21 dias pós-lesão. As MSC não estavam presentes no local da lesão e a avaliação por imunofluorescência demonstrou atenuação significativa da resposta inflamatória com redução em macrófagos marcados com anticorpo anti CD68 (ED1), diminuição da imunorreatividade de astrócitos (GFAP +) e maior ativação das células-tronco endógenas (nestin+) nos grupos tratados. Assim, o transplante de células teve efeito positivo sobre a recuperação de lesão traumática da medula espinal, possivelmente devido ao potencial das MSCs para atenuar a resposta imunológica. Palavras-chave: Células-tronco. Neurocirurgia. Terapia celular.

The effect of microglial ablation and mesenchymal stem cell transplantation on a cuprizone‐induced demyelination model

“…However, MSC transplantation attenuated astrocytosis in the CPZ model. In keeping with our study, Araujo et al (2016) showed that damages to the CNS elevated the intensity astrocytic marker (GFAP). Explained as fibrillar reactive astrocytosis, this is related to hyperplasia and hypertrophy of astrocytes.…”

“…Explained as fibrillar reactive astrocytosis, this is related to hyperplasia and hypertrophy of astrocytes. The reactive astrocytes derived from the glial scar accumulates around the lesion, forming a physical barrier and an inhibitory environment for axonal regeneration and remyelination (Araujo et al, 2016). The significant reduction was observed in astrocytes of the MSC‐treated animals suggests that MSC can undermine the astrocytes response and mitigate the effects of scar tissue formation on providing a suitable environment for remyelination.…”