Mesenchymal stem cell transplantation reduces glial cyst and improves functional outcome following spinal cord compression.
ABSTRACT OBJECTIVE: Mesenchymal stem cells (MSCs) are multipotent stem cells that play a supportive role in regenerative therapies, especially in the CNS where spontaneous regeneration is limited. MSCs can exert a paracrine activity and modulate the inflammatory response after a CNS injury, Spinal cord injury (SCI) leads to permanent neurological deficits below the injury site, due to neuronal and axonal damage. Among the experimental treatments following SCI, cell transplantation emerged as a promising approach. METHODS: We used a compression injury model in the mouse spinal cord and we acutely transplanted MSCs into the lesion cavity; injured mice without the graft served as controls. After 26 days we investigated the survival of MSCs and evaluated their effect on the formation of the glial cyst and on injury-related inflammation. RESULTS: Grafted MSCs remained permanently undifferentiated. In MSC-treated mice the lesion volume was reduced by 31.6%, compared to control mice, despite astroglial and microglial activation was not altered by graft. Moreover sensory and motor tests demonstrated that MSC cell therapy results in improvement on a battery of behavioural tests, in comparison to control mice: in detail, MSC-treated mice vs control ones respectively registered the score 0.00 vs 0.50 in the posture test, 0.00 vs 1.50 in the hindlimb flexion test, 3.00 vs 2.25 in the sensory test, and finally 7.50 mistakes vs 15.83, respectively, in the foot-fault test. CONCLUSION: Our results underscore the therapeutic potential of MSCs, making them promising candidates for CNS pathologies.
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ABSTRACT: Spinal cord injury (SCI) triggers inflammation with activation of innate immune responses that contribute to secondary injury including oligodendrocyte apoptosis, demyelination, axonal degeneration, and neuronal death. Macrophage activation, accumulation, and persistent inflammation occur in SCI. Macrophages are heterogeneous cells with extensive functional plasticity and have the capacity to switch phenotypes by factors present in the inflammatory microenvironment of the injured spinal cord. This review will discuss the role of different polarized macrophages and the potential effect of macrophage-based therapies for SCI.Neural Plasticity 01/2013; 2013:945034. · 2.86 Impact Factor
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ABSTRACT: It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs) through the cerebrospinal fluid (CSF) has beneficial effects on acute spinal cord injury (SCI) in rats. The present study examined whether BMSC infusion into the CSF is effective for subacute (1- and 2-week post-injury), and/or chronic (4-week post-injury) SCI in rats. The spinal cord was contused by dropping a weight at the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same strain were injected three times (once weekly) into the CSF through the fourth ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial injection, the average BBB score for locomotor assessment increased from 1.0-3.5 points before injection to 9.0-10.9 points in the BMSC-injection subgroups, while, in the PBS (vehicle)-injection subgroups, it increased only from 0.5-4.0 points before injection to 3.0-5.1 points. Numerous axons associated with Schwann cells extended longitudinally through the connective tissue matrices in the astrocyte-devoid lesion without being blocked at either the rostral or the caudal borders in the BMSC-injection subgroups. A small number of BMSCs were found to survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and the neurite extension of cultured neurons more effectively than did the PBS-injected CSF. These results indicate that BMSCs had beneficial effects on locomotor improvement as well as on axonal regeneration in both subacute and chronic SCI rats, and the results also suggest that BMSCs might function as neurotrophic sources via the CSF.PLoS ONE 01/2013; 8(9):e73494. · 3.53 Impact Factor
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ABSTRACT: Mesenchymal stem cell (MSC) therapy has attracted the attention of scientists and clinicians around the world. Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve injury. These effects are believed to be due to their ability to differentiate into other cell lineages, modulate inflammatory and immunomodulatory responses, reduce cell apoptosis, secrete several neurotrophic factors and respond to tissue injury, among others. There are many pre-clinical studies on MSC treatment for spinal cord injury (SCI) and peripheral nerve injuries. However, the same is not true for clinical trials, particularly those concerned with nerve trauma, indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve lesions. As for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental studies. For these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive outcomes. This review is based on pre-clinical studies and clinical trials available in the literature from 2010 until now. At the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves, respectively.World journal of stem cells. 04/2014; 6(2):179-194.