Homologous Transplantation of Neural Stem Cells to the Injured Spinal Cord of Mice

Pallini, Roberto; Vitiani, Lucia Ricci; Bez, Alessandra; Casalbore, Patrizia; Facchiano, Francesco; Gerevini, V. Di Giorgi; Falchetti, Maria Laura; Fernández, Eduardo B.; Maira, Giulio; Peschle, Cesare; Parati, Eugenio

doi:10.1227/01.neu.0000180058.58372.4c

Cited by 58 publications

(45 citation statements)

References 53 publications

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“…Research activities focusing on NSC have shown that promoting their proliferation or grafting/infusing them by different routes into the brain leads to neurological improvement in different brain disease models, including stroke (Nomura et al, 2005;Pallini et al, 2005;Capone et al, 2007;Maysami et al, 2008). This benefit does not come only by their capacity to replace lost neurons.…”

Section: Discussionmentioning

confidence: 99%

Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke

Blondeau

Nguemeni

Debruyne

et al. 2009

Neuropsychopharmacol

116

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Omega-3 polyunsaturated fatty acids are known to have therapeutic potential in several neurological and psychiatric disorders. However, the molecular mechanisms of action underlying these effects are not well elucidated. We previously showed that alpha-linolenic acid (ALA) reduced ischemic brain damage after a single treatment. To follow-up this finding, we investigated whether subchronic ALA treatment promoted neuronal plasticity. Three sequential injections with a neuroprotective dose of ALA increased neurogenesis and expression of key proteins involved in synaptic functions, namely, synaptophysin-1, VAMP-2, and SNAP-25, as well as proteins supporting glutamatergic neurotransmission, namely, V-GLUT1 and V-GLUT2. These effects were correlated with an increase in brain-derived neurotrophic factor (BDNF) protein levels, both in vitro using neural stem cells and hippocampal cultures and in vivo, after subchronic ALA treatment. Given that BDNF has antidepressant activity, this led us to test whether subchronic ALA treatment could produce antidepressant-like behavior. ALA-treated mice had significantly reduced measures of depressive-like behavior compared with vehicletreated animals, suggesting another aspect of ALA treatment that could stimulate functional stroke recovery by potentially combining acute neuroprotection with long-term repair/compensatory plasticity. Indeed, three sequential injections of ALA enhanced protection, either as a pretreatment, wherein it reduced post-ischemic infarct volume 24 h after a 1-hour occlusion of the middle cerebral artery or as post-treatment therapy, wherein it augmented animal survival rates by threefold 10 days after ischemia.

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Section: Discussionmentioning

confidence: 99%

Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke

Blondeau

Nguemeni

Debruyne

et al. 2009

Neuropsychopharmacol

116

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“…Compared with observational open field methods, which monitor the animals' reluctance to move about in an open field arena and have been used in similar studies, the footprint analysis provides a more reliable assessment of hindlimb movements (Goldberger et al, 1990;Hamers et al, 2001;Hamers et al, 2006;Kunkel-Bagden et al, 1993;Pallini et al, 2005). Mice transplanted with either EVNPCs (n8) or T4as-NPCs (n8), recovered a stepping gait one week after spinal cord injury, whereas animals that received vehicle injection (n8) experienced this recovery after 2 weeks ( Fig.…”

Section: Journal Of Cell Science 122 (22)mentioning

confidence: 99%

“…Here we refer to neural stem cells and their progeny, progenitor cells, as NPCs. NPCs might be directed to a neuronal lineage and used to restore the function of damaged neurons in cases of neurodegenerative disorders and injuries of the brain or spinal cord (Cao et al, 2002;Pallini et al, 2005;Pluchino et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of thymosin β4 in neural progenitor grafts promotes spinal cord regeneration

Mollinari

Ricci–Vitiani

Pieri

et al. 2009

Journal of Cell Science

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Thymosin β4 (Tβ4) is an actin-binding peptide whose expression in developing brain correlates with migration and neurite extension of neurons. Here, we studied the effects of the downregulation of Tβ4 expression on growth and differentiation of murine neural progenitor cells (NPCs), using an antisense lentiviral vector. In differentiation-promoting medium, we found twice the number of neurons derived from the Tβ4-antisense-transduced NPCs, which showed enhanced neurite outgrowth accompanied by increased expression of the adhesion complex N-cadherin–β-catenin and increased ERK activation. Importantly, when the Tβ4-antisense-transduced NPCs were transplanted in vivo into a mouse model of spinal cord injury, they promoted a significantly greater functional recovery. Locomotory recovery correlated with increased expression of the regeneration-promoting cell adhesion molecule L1 by the grafted Tβ4-antisense-transduced NPCs. This resulted in an increased number of regenerating axons and in sprouting of serotonergic fibers surrounding and contacting the Tβ4-antisense-transduced NPCs grafted into the lesion site. In conclusion, our data identify a new role for Tβ4 in neuronal differentiation of NPCs by regulating fate determination and process outgrowth. Moreover, NPCs with reduced Tβ4 levels generate an L1-enriched environment in the lesioned spinal cord that favors growth and sprouting of spared host axons and enhances the endogenous tissue-repair processes.

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“…[5][6][7][8] In recent years, gene therapy has provided an exciting new direction for research, and substantial progress has been made with improved vectors. Viral vectors have a high transfection efficiency, but their application is restricted because they are cytotoxic with high immunogenicity.…”

mentioning

confidence: 99%

Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

Song¹,

Wang

Shen³

et al. 2017

IJN

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Background Spinal cord injuries (SCIs) can cause severe disability or death. Treatment options include surgical intervention, drug therapy, and stem cell transplantation. However, the efficacy of these methods for functional recovery remains unsatisfactory. Purpose This study was conducted to explore the effect of ultrasound (US)-mediated destruction of poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs) expressing nerve growth factor (NGF) ( NGF /PLGA NBs) on nerve regeneration in rats following SCI. Materials and methods Adult male Sprague Dawley rats were randomly divided into four treatment groups after Allen hit models of SCI were established. The groups were normal saline (NS) group, NGF and NBs group, NGF and US group, and NGF /PLGA NBs and US group. Histological changes after SCI were observed by hematoxylin and eosin staining. Neuron viability was determined by Nissl staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was used to examine cell apoptosis. NGF gene and protein expressions were detected by quantitative reverse transcription polymerase chain reaction and Western blotting. Green fluorescent protein expression in the spinal cord was examined using an inverted fluorescence microscope. The recovery of neural function was determined using the Basso, Beattie, and Bresnahan test. Results NGF therapy using US-mediated NGF /PLGA NBs destruction significantly increased NGF expression, attenuated histological injury, decreased neuron loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in rats with SCI. Conclusion US-mediated NGF /PLGA NBs destruction effectively transfects the NGF gene into target tissues and has a significant effect on the injured spinal cord. The combination of US irradiation and gene therapy through NGF /PLGA NBs holds great promise for the future of nanomedicine and the development of noninvasive treatment options for SCI and other diseases.

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Homologous Transplantation of Neural Stem Cells to the Injured Spinal Cord of Mice

Cited by 58 publications

References 53 publications

Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke

Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke

Downregulation of thymosin β4 in neural progenitor grafts promotes spinal cord regeneration

Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

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