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3.
Stem Cell Res Ther ; 6: 211, 2015 Nov 04.
Article in English | MEDLINE | ID: mdl-26530515

ABSTRACT

INTRODUCTION: Stem cells from adult tissues were considered for a long time as promising tools for regenerative therapy of neurological diseases, including spinal cord injuries (SCI). Indeed, mesenchymal (MSCs) and neural crest stem cells (NCSCs) together constitute the bone marrow stromal stem cells (BMSCs) that were used as therapeutic options in various models of experimental SCI. However, as clinical approaches remained disappointing, we thought that reducing BMSC heterogeneity should be a potential way to improve treatment efficiency and reproducibility. METHODS: We investigated the impact of pure populations of MSCs and NCSCs isolated from adult bone marrow in a mouse model of spinal cord injury. We then analyzed the secretome of both MSCs and NCSCs, and its effect on macrophage migration in vitro. RESULTS: We first observed that both cell types induced motor recovery in mice, and modified the inflammatory reaction in the lesion site. We also demonstrated that NCSCs but especially MSCs were able to secrete chemokines and attract macrophages in vitro. Finally, it appears that MSC injection in the spinal cord enhance early inflammatory events in the blood and spinal cord of SCI mice. CONCLUSIONS: Altogether, our results suggest that both cell types have beneficial effects in experimental SCI, and that further investigation should be dedicated to the regulation of the inflammatory reaction following SCI, in the context of stem cell-based therapy but also in the early-phase clinical management of SCI patients.


Subject(s)
Chemotaxis , Mesenchymal Stem Cell Transplantation , Spinal Cord Injuries/therapy , Animals , Chemokines/metabolism , Female , Mesenchymal Stem Cells/physiology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Motor Activity , Nerve Regeneration , Neural Crest/cytology , Neural Stem Cells/physiology , RAW 264.7 Cells , Recovery of Function , Regenerative Medicine , Reproducibility of Results , Spinal Cord/immunology , Spinal Cord/physiology , Spinal Cord Injuries/immunology
4.
PLoS One ; 8(5): e64723, 2013.
Article in English | MEDLINE | ID: mdl-23741377

ABSTRACT

Adult bone marrow stroma contains multipotent stem cells (BMSC) that are a mixed population of mesenchymal and neural-crest derived stem cells. Both cells are endowed with in vitro multi-lineage differentiation abilities, then constituting an attractive and easy-available source of material for cell therapy in neurological disorders. Whereas the in vivo integration and differentiation of BMSC in neurons into the central nervous system is currently matter of debate, we report here that once injected into the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, pure populations of either bone marrow neural crest stem cells (NCSC) or mesenchymal stem cells (MSC) survived only transiently into the lesioned brain. Moreover, they do not migrate through the brain tissue, neither modify their initial phenotype, while no recovery of the dopaminergic system integrity was observed. Consequently, we tend to conclude that MSC/NCSC are not able to replace lost neurons in acute MPTP-lesioned dopaminergic system through a suitable integration and/or differentiation process. Altogether with recent data, it appears that neuroprotective, neurotrophic and anti-inflammatory features characterizing BMSC are of greater interest as regards CNS lesions management.


Subject(s)
Bone Marrow Cells/cytology , Brain Injuries/therapy , Mesenchymal Stem Cells/cytology , Neural Stem Cells/cytology , Stem Cell Transplantation , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Bone Marrow Cells/physiology , Brain Injuries/chemically induced , Brain Injuries/pathology , Cell Death , Dopaminergic Neurons/pathology , Mesenchymal Stem Cells/physiology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neural Stem Cells/physiology , Treatment Failure
5.
J Neurosci Res ; 90(12): 2317-27, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22847229

ABSTRACT

Synaptic vesicle protein 2 (SV2) is a glycoprotein that exists in three isoforms, SV2A, SV2B, and SV2C. SV2A knockout (KO) mice and SV2A/SV2B double KO (DKO) mice, but not SV2B KO animals, start to experience severe seizures and weight loss 7 days after birth and die at about postnatal day (P)14-P23. Because excitatory and inhibitory inputs play a major role in controlling neuronal excitability in the hippocampus, we examined the effects of SV2A and/or SV2B deletions on glutamatergic and GABA(A) neurotransmission in hippocampal CA1 pyramidal neurons. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, mEPSCs, sIPSCs, and mIPSCs, respectively) were recorded using the whole-cell patch-clamp technique in slices from P6-P14 mice. The frequency of sEPSCs was increased in SV2A KO and SV2A/SV2B DKO mice, but their amplitude was unchanged. Such changes were not observed in SV2B KOs. On the contrary, the frequency and amplitude of sIPSCs were decreased in SV2A KO and SV2A/SV2B DKO mice but not in SV2B KO animals, as reported previously for the CA3 region. Kinetic parameters of sIPSCs and sEPSCs were unchanged. Importantly, no changes were observed in any genotype when examining mEPSCs and mIPSCs. We conclude that action potential- and Ca(2+) -dependent glutamatergic and GABAergic synaptic transmission are differentially altered in the hippocampus of SV2A-deficient mice, whereas the mechanism of exocytosis itself is not changed. The altered balance between these major excitatory and inhibitory inputs is probably a contributing factor to seizures in SV2A KO and SV2A/SV2B DKO mice.


Subject(s)
CA1 Region, Hippocampal/cytology , Excitatory Postsynaptic Potentials/physiology , Inhibitory Postsynaptic Potentials/physiology , Membrane Glycoproteins/deficiency , Nerve Tissue Proteins/deficiency , Pyramidal Cells/physiology , Action Potentials , Animals , Calcium Signaling , Genes, Lethal , Glutamic Acid/physiology , Membrane Glycoproteins/genetics , Membrane Glycoproteins/physiology , Mice , Mice, Knockout , Mice, Transgenic , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/physiology , Patch-Clamp Techniques , Protein Isoforms/physiology , Synaptic Vesicles/metabolism
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