References of "Rogister, Bernard"
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See detailOsteopontin predicts radiotherapy response of glioblastoma patients : new role in DNA damage repair
Henry, Aurélie ULg; Nokin, Marie-Julie; Leroi, Natacha ULg et al

Conference (2016, March 22)

- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These ... [more ▼]

- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments include maximal surgical resection, radiotherapy and concomitant or adjuvant chemotherapy with Temozolomide. However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. GBM-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, high osteopontin (OPN) expression correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. Our recent study (Lamour V and Henry A, IJC 2015) has demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem characters. In the continuation of this work, our recent studies focused on the potential role of OPN in the resistance of GBM cells to radiotherapy and its potential implication in the initiation of Double Strand Breaks (DSBs) repair mechanisms. - Aims: In the context of this study, different GBM cell lines (U251-MG, U87-MG and U87 Viii) were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation. - Methods and results: We performed the transient transfection of different GBM cell lines (U251-MG, U87-MG and U87-MG overexpressing EGFR VIII) with siRNAs specifically directed against OPN. After irradiation, all these OPN-depleted cells consistently showed a lower induction of γ–H2AX compared to control (irrelevant siRNA) as evidenced by western blot and immunofluorescence techniques. Thereafter, clonogenic assays allowed to prove that the survival of OPN-depleted cells was affected after an exposure to irradiation. To assess the importance of OPN expression in the response to radiotherapy, an heterotopic xenograft model was used. In brief, IPTG-inducible U87 shOPN clones were injected subcutaneously in NOD-SCID mice and were allowed to form a tumor. When average tumor volume reached a predetermined size range, mice were treated (or not) with IPTG by intraperitoneal injection during five days. At the end of the treatment, tumors were selectively exposed to gamma-irradiation by using a small animal irradiator X-RAD 225Cx (Precision X-Ray Inc., North Branford, CT). One week later, mice were sacrificed and tumors were measured. In this pilot study, we observed that mice in which the tumor was depleted in OPN displayed a slight regression in the tumor growth compared to mice that received radiotherapy alone (no IPTG), where the tumor volume remained constant. - Conclusions: Taken together, these preliminary data meet the fact that OPN is important in the response of GBM to radiotherapy. The in vitro results converge to the fact that OPN might be implicated in the initiation of the DSBs repair following irradiation. Currently, we would like to investigate this hypothesis in vivo but also to check the effect of OPN depletion combined to radiotherapy on the survival of mice in an orthotopic xenograft model. [less ▲]

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See detailHDAC7 inhibition resets STAT3 tumorigenic activity in human glioblastoma independently of EGFR and PTEN: new opportunities for selected targeted therapies
Peixoto, Paul; Blomme, Arnaud; Costanza, Brunella ULg et al

in Oncogene (2016)

To date, the mutational status of EGFR and PTEN has been shown as relevant for favoring pro- or anti-tumor functions of STAT3 in human glioblastoma multiforme (GBM). We have screened genomic data from 154 ... [more ▼]

To date, the mutational status of EGFR and PTEN has been shown as relevant for favoring pro- or anti-tumor functions of STAT3 in human glioblastoma multiforme (GBM). We have screened genomic data from 154 patients and have identified a strong positive correlation between STAT3 and HDAC7 expression. In the current work we show the existence of a subpopulation of patients overexpressing HDAC7 and STAT3 that has particularly poor clinical outcome. Surprisingly, the somatic mutation rate of both STAT3 and HDAC7 was insignificant in GBM comparing with EGFR, PTEN or TP53. Depletion of HDAC7 in a range of GBM cells induced the expression of tyrosine kinase JAK1 and the tumor suppressor AKAP12. Both proteins synergistically sustained the activity of STAT3 by inducing its phosphorylation (JAK1) and protein expression (AKAP12). In absence of HDAC7, activated STAT3 was responsible for significant imbalance of secreted pro-/anti-angiogenic factors. This inhibited the migration and sprouting of endothelial cells in paracrine fashion in vitro as well as angiogenesis in vivo. In a murine model of GBM, induced HDAC7-silencing decreased the tumor burden by threefold. The current data show for the first time that silencing HDAC7 can reset the tumor suppressor activity of STAT3, independently of the EGFR/PTEN/TP53 background of the GBM. This effect could be exploited to overcome tumor heterogeneity and provide a new rationale behind the development of specific HDAC7 inhibitors for clinical use. [less ▲]

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See detailHuman Adult Bone Marrow and Adipose Tissue Harbor Stem Cells with Neural Crest Characteristics.
Coste, Cécile ULg; Neirinckx, Virginie; Rogister, Bernard ULg et al

Poster (2015, December 03)

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See detailAdult bone marrow mesenchymal and neural crest stem cells are chemoattractive and accelerate motor recovery in a mouse model of spinal cord injury
Neirinckx, Virginie ULg; Agirman, Gulistan ULg; Coste, Cécile ULg et al

in Stem Cell Research and Therapy (2015), 6(211),

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 ... [more ▼]

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. [less ▲]

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See detailOsteopontin as a new target in glioblastoma progression and resistance to radiotherapy
Henry, Aurélie ULg; Bellahcene, Akeila ULg; Castronovo, Vincenzo ULg et al

Conference (2015, September 10)

Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments ... [more ▼]

Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments include maximal surgical resection, radiotherapy and concomitant or adjuvant chemotherapy with Temozolomide (TMZ). However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. Glioblastoma-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, osteopontin (OPN) ranks correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. OPN expression is largely considered as a molecular cancer marker associated with poor prognosis for patients with cancer. Our preliminary works (Lamour V and Henry A, IJC 2015) have demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem charachters. Within the continuance of this work, our recent studies focused on the potential role of OPN in the resistance of glioblastoma cells to radiotherapy and its implication in the initiation of Double Strand Breaks (DSBs) repair mechanism. In this context, U251-MG and U87-MG cells were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation (γ–IR). The transient transfection of both cell lines with siRNA directed against OPN shown a lower induction of γ–H2AX compared to control (irrelevant siRNA). The survival of U251-OPN depleted cells was also affected after an exposure to γ–IR (based on clonogenic assays). However, the sole depletion of OPN in U87 cells affected their survival (independently of the γ–IR). To prove that the secreted form of OPN is necessary to survive after γ–IR, conditionned medium of U87-shSCR clones (rich in OPN) was used to treat U87shOPN clones before an exposure to γ–IR. By immunofluorescence, we observed that the γ–H2AX staining was higher in U87 shOPN clones than when treated with their own conditionned medium (poor in OPN). Currently, we are investigating the in vivo implication of OPN in the initiation of DSBs repair mechanism after an exposure of mice to γ–IR (whole brain exposure). For this purpose, IPTG-inducible U87 shRNA clones (SCR and OPN) have been generated and validated for an orthotopic xenograft model in NOD-SCID mice. The survival after a radiotherapy of 10 Gy (2Gy per day for 5 days) will be assessed in OPN-positive and –negative tumor-bearing mice. Taken together, these datas suggest that OPN could represent an important pronostic factor for patient response to radiotherapy in the context of GBM. [less ▲]

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See detailEVALUATION OF SV2Alox/Cre TRANSGENIC MOUSE USING [18F]UCB-H IN IN VITRO AUTORADIOGRAPHY
Serrano Navacerrada, Maria Elisa ULg; Becker, Guillaume ULg; MENTEN, Catherine ULg et al

Poster (2015, September 04)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking. Interestingly, the SV2A has been identify as the binding site for ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking. Interestingly, the SV2A has been identify as the binding site for the antiepileptic drug levetiracetam, showing a close relation between the epilepsy, the dysregulation of the SV2A levels and the response to antiepileptic medications. SV2A floxed-mice were developed using a cre-lox technique, leading to a strong decrease of SV2A expression in the CA3 field of the hippocampus. We aim here to validate this model using [18F]UCB-H, a novel PET imaging radiotracer with a nanomolar affinity for human SV2A. Methods: In vitro autoradiography were performed on SV2Alox/Cre+ transgenic mouse brain slices. SV2Alox/Cre- mouse was used as control. To obtain a structural reference, brain slices underwent eosin-haematoxylin staining. Images of both procedures were coregistered using π-PMOD software. Regions of interest (Dentate Gyrus, CA1, CA2 and CA3) were drawn according to a stereotaxic atlas of the mouse brain. Results: Analyses showed significant differences in radiotracer binding (p<0.001) between SV2Alox/Cre+ mouse and SV2Alox/Cre- mouse highlighting an important reduction for the labelling density in Ammon's horn, particularly in CA1, compared to Dentate Gyrus where the diminution was less marked. Conclusions: Here, we used the radiotracer [18F]UCB-H to probe the decreased expression of SV2A protein in the hippocampus of SV2Alox/Cre+ mouse versus SV2Alox/Cre- control mouse. Our results contribute to the validation of the model, and encourage us to proceed with further longitudinal and behavioural studies. [less ▲]

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See detailAre neural crest stem cells the missing link between hematopoietic and neurogenic niches?
Coste, Cécile ULg; Neirinckx, Virginie ULg; Gothot, André ULg et al

in Frontiers in Cellular Neuroscience (2015)

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See detailDifferential membrane marker expression in adult rodent bone marrow mesenchymal and neural crest stem cells.
Wislet, Sabine ULg; Coste, Cécile ULg; Neirinckx, Virginie ULg et al

Poster (2015, March)

Bone marrow stem cells are endowed with in vitro multi-lineage differentiation abilities, and constitute an attractive autologous source of material for cell therapy. With regards to recent findings ... [more ▼]

Bone marrow stem cells are endowed with in vitro multi-lineage differentiation abilities, and constitute an attractive autologous source of material for cell therapy. With regards to recent findings, adult mesenchymal stem cells (MSC) are commonly assimilated to neural crest stem cells (NCSC), both isolated from adult bone marrow. The objective of this study was therefore to highlight significant differences for membrane markers between those two cell types. Using the minimal criteria for defining multipotent mesenchymal stromal cells as previously described by The International Society for Cellular Therapy, we were quite surprised that no significant difference could discriminate MSC from NCSC. To define new markers, we first performed a microarray comparison. Based on those results, we validated selected targets by RT-PCR, then by immunocytochemistry. In parallel, we observed that NCSC had the unique property (compared to MSC) to grow as spheres, which could also be used as a purification protocol for NCSC from adult bone marrow. Altogether, we demonstrated that P75NTR was the most significant discriminating marker between MSC and NCSC, isolated from mouse adult bone marrow, which could be used as selecting marker in an enrichment protocol. Sphere formation could then be used as a purification protocol for NCSC. [less ▲]

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See detailTargeting osteopontin suppresses glioblastoma stem-like cell character and tumorigenicity in vivo
Lamour, Virginie; Henry, Aurélie ULg; Kroonen, Jerome et al

in International Journal of Cancer = Journal International du Cancer (2015)

Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported in multiple types of cancer including ... [more ▼]

Osteopontin (OPN) is a secreted protein involved in most aspects of tumor progression and metastasis development. Elevated OPN expression has been reported in multiple types of cancer including glioblastoma (GBM), the highest grade and most aggressive brain tumor. GBMs contain a subpopulation of glioma-initiating cells (GICs) implicated in progression, therapeutic resistance and recurrence. We have previously demonstrated that OPN silencing inhibited GBM cell growth in vitro and in vivo. Moreover, activation of CD44 signaling upon OPN ligation has been recently implicated in the acquisition of a stem cell phenotype by GBM cells. The present study is aimed to explore OPN autocrine function using shRNA silencing strategy in GICs enriched from GBM cell lines and a human primary GBM grown in EGF and bFGF defined medium. The removal of these growth factors and addition of serum induced a significant loss of OPN expression in GICs. We showed that OPN-silenced GICs were unable to grow as spheres and this capacity was restored by exogenous OPN. Importantly, the expression of Sox2, Oct3/4 and Nanog, key stemness transcription factors, was significantly decreased in GICs upon OPN targeting. We identified Akt/mTOR/p70S6K as the main signaling pathway triggered following OPN-mediated EGFR activation in GICs. Finally, in an orthotopic xenograft mouse model, the tumorigenic potential of U87-MG sphere cells was completely abrogated upon OPN silencing. Our demonstration of endogenous OPN major regulatory effects on GICs stemness phenotype and tumorigenicity implies a greater role than anticipated for OPN in GBM pathogenesis from initiation and progression to probable recurrence. [less ▲]

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See detailAdult mouse sub-ventricular zones stimulate glioblastoma stem cells specific invasion through CXCL12/CXCR4 signaling
Goffart, Nicolas ULg; Kroonen, Jérome; Di Valentin, Emmanuel ULg et al

in Journal of Neuro-Oncology (2015), 17(1), 81-94

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See detailGlioblastoma Circulating Cells: Reality, Trap or Illusion?
LOMBARD, Arnaud ULg; Goffart, Nicolas ULg; Rogister, Bernard ULg

in Stem Cells International (2015)

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See detailSpecific properties of bone marrow mesenchymal and neural crest-derived stem cells: Relevance in spinal cord injury therapy.
Neirinckx, Virginie ULg; Agirman, Gulistan ULg; Marquet, Alice ULg et al

Poster (2014, November 17)

Spinal cord injury (SCI) treatment represents a critical issue in clinical research and patient care. Stem cell-based replacement therapies have already been proposed worldwide, especially studying stem ... [more ▼]

Spinal cord injury (SCI) treatment represents a critical issue in clinical research and patient care. Stem cell-based replacement therapies have already been proposed worldwide, especially studying stem cells from the adult bone marrow stroma. Previous studies focusing on those cells did not specifically consider their intrinsic embryonic heterogeneity, thus intermingling different stem cells subpopulations to treat experimental SCI or even injured patients. In this study, we decided to compare adult bone marrow neural crest-derived stem cells (NCSC) and mesenchymal stem cells (MSC), and highlight which of their specific properties could be relevant in therapeutic perspectives. In that purpose, we compared NCSC and MSC isolated from adult mouse bone marrow. We then compared the effects that both cell types could exert once grafted inside an injured spinal cord. Cells were injected into the spinal cord of mice that right after a spinal cord contusion at the T11-12 spinal level. Our results indicate that both MSC and NCSC-injected mice recovered locomotion abilities faster than control mice (as assessed by BMS scoring). Additionally, we observed that after 28 days post-injury, the lesion volume tended to decrease in mice that received cell graft compared to control group. Interestingly, it appeared that MSC seemed to be able to modulate inflammation inside the lesion, more than NCSC. Indeed, MSC-graft increased early neutrophil and macrophage recruitment in the bloodstream and inside the spinal cord, and increased the number of arginase-1-expressing cells remaining in the spinal cord after 28 days. In parallel, we compared the secretome of both NCSC and MSC, and noticed some interesting differences: MSC secreted several chemokines reflecting possible immunomodulating properties, while NCSC secreted products might be able to enhance neurite outgrowth. Indeed, preliminary data showed that NCSC induced neuritogenesis on primary neurons in vitro. Altogether, those results should help to improve and optimize cell-based therapies parameters and/or to define precise and efficient pharmacological treatments for SCI patients. [less ▲]

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See detailGlioblastoma stem cells: new insights in therapeutic strategies
Goffart, Nicolas ULg; Dedobbeleer, Matthias ULg; Rogister, Bernard ULg

in Future Neurology (2014), 9(6), 639-653

Despite notable achievements in glioblastoma diagnosis and treatment, the prognosis of glioblastoma patients remains poor and reflects the failure of current therapeutic modalities. In this context ... [more ▼]

Despite notable achievements in glioblastoma diagnosis and treatment, the prognosis of glioblastoma patients remains poor and reflects the failure of current therapeutic modalities. In this context, innovative therapeutic strategies have recently been developed to specifically target glioblastoma stem cells, a subpopulation of tumor cells involved in experimental tumorigenesis and known to be critical for tumor recurrence and therapeutic resistance. The current review summarizes the different trails which make glioblastoma stem cells resistant to treatments, mainly focusing on radio-, chemo- and immunotherapy. This broad overview might actually help to set up new bases for glioblastoma therapy in order to better fight tumor relapses and to improve the patients’ prognosis. [less ▲]

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See detailEccentric muscle contractions: risks and benefits
Hody, Stéphanie ULg; Croisier, Jean-Louis ULg; Lacrosse, Zoé ULg et al

in Proceedings of the Belgian Royal Academies of Medicine (2014)

La contraction musculaire excentrique se caractérise par le développement d'une tension musculaire associée à l'étirement concomitant du complexe musculo-tendineux. Ce mode de contraction présente un ... [more ▼]

La contraction musculaire excentrique se caractérise par le développement d'une tension musculaire associée à l'étirement concomitant du complexe musculo-tendineux. Ce mode de contraction présente un intérêt croissant dans de nombreux domaines tels que l’entraînement sportif, la médecine physique et la rééducation. De plus, certaines indications de l’entraînement en mode excentrique ont été posées chez des patients porteurs de maladies chroniques. Cependant, lorsqu’il est réalisé de manière intense et inhabituelle, l’exercice excentrique peut entraîner diverses altérations de l’ultrastructure musculaire qui se manifestent par une série de symptômes cliniques comme des douleurs musculaires d’apparition retardées (Delayed-Onset Muscle Soreness, DOMS) et une altération de la fonction musculaire. Malgré la littérature abondante consacrée à la description du phénomène des DOMS, aucune théorie cohérente n’est actuellement disponible pour expliquer la survenue différée des sensations douloureuses et des signes associés. De même, toujours à l’analyse de la littérature, on ne peut que constater l’absence de solution thérapeutique susceptible d’atténuer significativement l’intensité des DOMS et de leurs conséquences fonctionnelles associées à l’exception, paradoxalement, de l’exercice excentrique lui-même qui, lorsqu’il est proposé en conditions sous-maximales d’intensité progressivement croissante, semble constituer la seule prévention réellement efficace de l’apparition des DOMS. De même, si l’efficacité d’un entraînement spécifique dans la prévention des DOMS a été confirmée par de nombreux travaux, la nature de cet effet protecteur reste sujette à conjectures. Nous sommes néanmoins convaincus qu’une meilleure compréhension des réponses aiguës et/ou adaptatives à l’exercice excentrique contribuerait d’une part, à la mise au point d’interventions thérapeutiques efficaces et d’autre part, à élucider les évènements moléculaires impliqués dans des conditions pathologiques telles que les myalgies et certaines maladies neuromusculaires. [less ▲]

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See detailBone marrow mesenchymal and neural crest-derived stem cells have distinct secretomes, which are both relevant for spinal cord injury therapy.
Neirinckx, Virginie ULg; Agirman, Gulistan ULg; Rogister, Bernard ULg et al

Conference (2014, September 25)

Objectives: Spinal cord injury (SCI) treatment represents a critical issue in clinical research and patient care. Stem cell-based replacement therapies have already been proposed worldwide, especially ... [more ▼]

Objectives: Spinal cord injury (SCI) treatment represents a critical issue in clinical research and patient care. Stem cell-based replacement therapies have already been proposed worldwide, especially studying stem cells from the adult bone marrow stroma. Previous studies focusing on those cells did not specifically consider their intrinsic embryonic heterogeneity, thus intermingling different stem cells subpopulations to treat experimental SCI or even injured patients. In this study, we decided to compare adult bone marrow neural crest-derived stem cells (NCSC) and mesenchymal stem cells (MSC), and highlight which of their specific properties could be relevant in therapeutic perspectives. Material and methods: In that purpose, we compared NCSC and MSC isolated from adult mouse bone marrow. We then compared the effects that both cell types could exert once grafted inside an injured spinal cord. Cells were injected into the spinal cord of mice that right after a spinal cord contusion at the T11-12 spinal level. Results: Both MSC and NCSC-injected mice recovered locomotion abilities faster than control mice (as assessed by BMS scoring). Additionally, we observed that after 28 days post-injury, the lesion volume tended to decrease in mice that received cell graft compared to control group. Interestingly, it appeared that MSC seemed to be able to modulate inflammation inside the lesion, more than NCSC. Indeed, MSC-graft increased early neutrophil and macrophage recruitment in the bloodstream and inside the spinal cord, and increased the number of arginase-1-expressing cells remaining in the spinal cord after 28 days. In parallel, we compared the secretome of both NCSC and MSC, and noticed some interesting differences: MSC secreted several chemokines reflecting possible immunomodulating properties, while NCSC secreted products might be able to enhance neurite outgrowth. Conclusions: Preliminary data showed that NCSC induced neuritogenesis on primary neurons in vitro. Altogether, those results should help to improve and optimize cell-based therapies parameters and/or to define precise and efficient pharmacological treatments for SCI patients. [less ▲]

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See detailNeutrophil contribution to spinal cord injury and repair
Neirinckx, Virginie ULg; Coste, Cécile ULg; Franzen, Rachelle ULg et al

in Journal of Neuroinflammation (2014), 11(1),

Spinal cord injuries remain a critical issue in experimental and clinical research nowadays, and it is now well accepted that the immune response and subsequent inflammatory reactions are of significant ... [more ▼]

Spinal cord injuries remain a critical issue in experimental and clinical research nowadays, and it is now well accepted that the immune response and subsequent inflammatory reactions are of significant importance in regulating the damage/repair balance after injury. The role of macrophages in such nervous system lesions now becomes clearer and their contribution in the wound healing process has been largely described in the last few years. Conversely, the contribution of neutrophils has traditionally been considered as detrimental and unfavorable to proper tissue regeneration, even if there are very few studies available on their precise impact in spinal cord lesions. Indeed, recent data show that neutrophils are required for promoting functional recovery after spinal cord trauma. In this review, we gathered recent evidence concerning the role of neutrophils in spinal cord injuries but also in some other neurological diseases, highlighting the need for further understanding the different mechanisms involved in spinal cord injury and repair. [less ▲]

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