Histological and Functional Benefit Following Transplantation of Motor Neuron Progenitors to the Injured Rat Spinal Cord

Rossi, Sharyn L.; Nistor, Gabriel; Wyatt, Tanya J.; Yin, Hong; Poole, Aleksandra J.; Weiss, John H.; Gardener, Matthew J.; Dijkstra, Sipke; Fischer, David F.; Keirstead, Hans S.

doi:10.1371/journal.pone.0011852

Cited by 98 publications

(92 citation statements)

References 42 publications

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“…Our results showed that MSC-treated group presented a greater amount of neural stem cells (nestin+) at the lesion site than the control. Thus, cell transplantation may have influenced the injure environment to provide signaling and growth factors to proliferation of endogenous stem cells as established by Urdzikova et al (2006) and Rossi et al (2010). Also, Wu et al (2003) demonstrated functional recovery after transplantation of MSC and attributed this to increased differentiation of endogenous neural stem cells.…”

Section: Discussionmentioning

confidence: 99%

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

Araújo

Carvalho

Paula

et al. 2016

SCA

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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.

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Section: Discussionmentioning

confidence: 99%

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

Araújo

Carvalho

Paula

et al. 2016

SCA

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“…To investigate whether TDP-43 fragments and/or mutant forms have cytotoxic or cytoprotective effects on mature motor neurons, human ES cell-derived motor neurons were generated in vitro as reported previously. 20 In addition to positive staining of HB-9 and Islet-1 (89.4 AE 4.0% and 88.8 AE 9.3%, respectively), immunocytochemistry showed that 88.3 AE 7.8% and 56.8 AE 20.7% of the cells expressed bIII-tubulin, a marker for neurons, and non-phosphorylated neurofilament protein, a marker for mature neurofilaments, respectively. Meanwhile, just 4.9 AE 3.2% of the cells expressed glial fibrillary acidic protein (GFAP), a marker for astrocytes (Fig.…”

Section: Resultsmentioning

confidence: 94%

Cellular toxicity induced by the 26‐kDa fragment and amyotrophic lateral sclerosis‐associated mutant forms of TAR DNA‐binding protein 43 in human embryonic stem cell‐derived motor neurons

Nishimoto

Okano

Imai

et al. 2013

Neurology & Clinical Neurosc

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Aims: Amyotrophic lateral sclerosis (ALS) results in the selective loss of motor neurons within several years of disease onset; however, the molecular mechanisms behind ALS pathogenesis remain largely unknown. Among the genes responsible for familial ALS, mutations in TAR DNA-binding protein 43 (TDP-43) have been identified. The present study evaluated the cytotoxicity of TDP-43 fragments and ALS-associated mutants against human embryonic stem cell-derived motor neurons. Methods: Magnetofection was used to investigate the mortality rates of motor neurons after forced expression of TDP-43 C-terminal fragments and ALS-associated TDP-43 missense mutants. Results: Neither wild-type TDP-43 nor the 35-kDa fragment induced cell death. However, the 26-kDa fragment, which forms insoluble aggregates in the motor neurons of ALS patients, showed significant cytotoxicity, similar to mutant forms of TDP-43, including p.A315T and p.A382T. Hence, a motor neuron-specific neurotoxic function might be attributed to both the 26-kDa fragment and the TDP-43 mutants. Thus, 26kDa C-terminal fragment was considered to play an important role in ALS pathology, but alterations in adenosine deaminase acting on RNA 2 (ADAR2) expression, an enzyme accountable for GluA2 (AMPA receptor subunit 2) mRNA editing insufficiency in sporadic ALS, did not lead to alterations in the expression of the 26-kDa fragment. Conclusions: This is the first report showing the influence of specific ALS-associated factors on the mortality of motor neurons through the manipulation of gene expression. The motor neuron disease model described herein might prove useful for the identification of novel pathogenic factors and neuroprotective agents for the treatment of ALS.

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“…Transplanted motor neurons may replace the lost MNs. Studies have shown that transplanted ESCs derived MNs supported the endogenous neurons survival through secretion of beneficial growth factors in the SCI model [27], spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS) model [28]. Transplanted OPCs may differentiate into mature oligodendrocytes to myelinate both ESCs derived MNs and constitutive MNs.…”

Section: Discussionmentioning

confidence: 99%

Myelination of Motor Neurons Derived from Mouse Embryonic Stem Cells by Oligodendrocytes Derived from Mouse Embryonic Stem Cells in a Microfluidic Compartmentalized Platform

Xiang¹,

Fisgin²,

Thakor³

2015

J Stem Cell Res Ther

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Histological and Functional Benefit Following Transplantation of Motor Neuron Progenitors to the Injured Rat Spinal Cord

Cited by 98 publications

References 42 publications

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

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

Cellular toxicity induced by the 26‐kDa fragment and amyotrophic lateral sclerosis‐associated mutant forms of TAR DNA‐binding protein 43 in human embryonic stem cell‐derived motor neurons

Myelination of Motor Neurons Derived from Mouse Embryonic Stem Cells by Oligodendrocytes Derived from Mouse Embryonic Stem Cells in a Microfluidic Compartmentalized Platform

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