References of "Franzen, Rachelle"
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See detailImpact model of spinal cord injury
Cantinieaux, Dorothée; Franzen, Rachelle ULg; Schoenen, Jean ULg

in Janowski, Miroslav (Ed.) Experimental Neurosurgery in Animal Models (2016)

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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 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 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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See detailEccentric training improves tendon biomechanical properties: a rat model
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent et al

in British Journal of Sports Medicine (2014, April), 48(7), 155

Background: Even if eccentric exercises appear favourable in primary prevention of tendons lesions and, especially, in secondary prevention after tendinopathy, the biomechanical changes to the tissue are ... [more ▼]

Background: Even if eccentric exercises appear favourable in primary prevention of tendons lesions and, especially, in secondary prevention after tendinopathy, the biomechanical changes to the tissue are not yet clear. Objective: We aimed to better define the biomechanical changes that affect healthy tendon after eccentric and concentric training. Design: Randomised controlled trial. Participants: Eighteen Sprague-Dawley rats of 2 months. Interventions: The six rats in the control group (U) were not subjected to physical exercise. The 12 remaining rats (6 in each group) ran on a treadmill set at a +15° incline for concentric training (C) or a -15° incline for eccentric training (E), at a speed of 17 m/min for 1 h, three times per week for 5 weeks. Main Outcome Measurements: The tricipital, patellar and Achilles tendons were subsequently removed to perform a traction test until rupture, and a histological analysis was performed. Results: There was a significant improvement in the rupture force of the patellar and tricipital tendons between the U and E groups. The tricipital tendons in the control group presented a significantly smaller cross-section than the E- and C-trained groups, but none between E and C groups. No significant difference was observed for the mechanical stress at rupture per surface unit between the three groups for all three tendons. However, a tendency towards improvement these values was observed between the trained and the U groups for the patellar tendon. Histological studies demonstrated the tendency of the development of a greater number of blood vessels and a larger quantity of collagen in the eccentric group. Conclusions: The mechanical properties of tendons in rats improve after specific training, especially following eccentric training. Our results partly explained how mechanical loading, especially in eccentric mode, could improve the tendon structure. [less ▲]

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See detailSpinal Cord Injuries – How Could Adult Mesenchymal and Neural Crest Stem Cells Take Up the Challenge?
Neirinckx, Virginie ULg; CANTINIEAUX, Dorothée ULg; Coste, Cécile ULg et al

in Stem Cells (2014)

Since several years, adult/perinatal mesenchymal and neural crest stem cells have been widely used to help experimental animal to recover from spinal cord injury. More interestingly, recent clinical ... [more ▼]

Since several years, adult/perinatal mesenchymal and neural crest stem cells have been widely used to help experimental animal to recover from spinal cord injury. More interestingly, recent clinical trials confirmed the beneficial effect of those stem cells, which improve functional score of patients suffering from such lesions. However, a complete understanding of the mechanisms of stem cell-induced recovery is seriously lacking. Indeed, spinal cord injuries gathered a wide range of biochemical and physiopathological events (such as inflammation, oxidative stress, axonal damage, demyelination, etc) and the genuine healing process after cell transplantation is not sufficiently defined. This review aims to sum up recent data about cell therapy in spinal cord lesions using mesenchymal or recently identified neural crest stem cells, by describing precisely which physiopathological parameter is affected and the exact processes underlying the observed changes. Overall, although significant advances are acknowledged, it seems that further deep mechanistic investigation is needed for the development of optimized and efficient cell-based therapy protocols. [less ▲]

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See detailBone marrow stromal stem cells transplantation in mice with acute spinal cord injury
Neirinckx, Virginie ULg; Rogister, Bernard ULg; Franzen, Rachelle ULg et al

in Methods in Molecular Biology (Clifton, N.J.) (2014), 1213

Spinal cord injured experimental animals are widely used for studying pathophysiological processes after central nervous system acute traumatic lesion and elaborating therapeutic solutions, some of them ... [more ▼]

Spinal cord injured experimental animals are widely used for studying pathophysiological processes after central nervous system acute traumatic lesion and elaborating therapeutic solutions, some of them based on stem cell transplantation. Here, we describe a protocol of spinal cord contusion in C57BL/6J mice, directly followed by bone marrow stromal stem cells transplantation. This model allows for the characterization of neuroprotective and neurorestorative abilities of these stem cells in a context of spinal cord trauma. [less ▲]

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See detailEccentric training improves tendon biomechanical properties: a rat model
Kaux, Jean-François ULg; Drion, Pierre ULg; Libertiaux, Vincent et al

in Journal of Orthopaedic Research (2013), 31(1), 119-124

Introduction: The treatment of choice for tendinopathies is eccentric reeducation. Although the clinical results appear favourable, the biomechanical changes to the tissue are not yet clear. Even if the ... [more ▼]

Introduction: The treatment of choice for tendinopathies is eccentric reeducation. Although the clinical results appear favourable, the biomechanical changes to the tissue are not yet clear. Even if the mechanotransduction theory is commonly accepted, the physiology of tendons is not clearly understood. We aimed to better define the biomechanical and histological changes that affect healthy tendon after eccentric and concentric training. Materiel and Methods: This study compared the effects of 2 methods of training (eccentric (E) training and concentric (C) training) with untrained (U) rats. The animals were trained over a period of 5 weeks. The tricipital, patellar and Achilles tendons were removed, measured and a tensile test until failure was performed. A histological analysis (hematoxylin and eosin and Masson's trichrome stains) was also realized. Results: There was a significant increase in the rupture force of the patellar and tricipital tendons between the U and E groups. The tricipital tendons in the control group presented a significantly smaller cross-sectional area than the E- and C-trained groups, but none was constated between E and C groups. No significant difference was observed for the mechanical stress between the three groups for all three tendons. Histological studies demonstrated the development of a greater number of blood vessels and a larger quantity of collagen in the E group. Discussion and conclusion: The mechanical properties of tendons in rats improve after specific training, especially following eccentric training. Our results partly explained how mechanical loading, especially in eccentric mode, could improve the healing of tendon. [less ▲]

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See detailConditioned Medium from Bone marrow-derived Mesenchymal Stem Cells improves recovery after Spinal Cord Injury in rats: an original strategy to avoid cell transplantation.
CANTINIEAUX, Dorothée ULg; QUERTAINMONT, Renaud; BLACHER, Silvia ULg et al

in PLoS ONE (2013), 8(8), 69515

Spinal cord injury triggers irreversible loss of motor and sensory functions. Numerous strategies aiming at repairing the injured spinal cord have been studied. Among them, the use of bone marrow-derived ... [more ▼]

Spinal cord injury triggers irreversible loss of motor and sensory functions. Numerous strategies aiming at repairing the injured spinal cord have been studied. Among them, the use of bone marrow-derived mesenchymal stem cells (BMSCs) is promising. Indeed, these cells possess interesting properties to modulate CNS environment and allow axon regeneration and functional recovery. Unfortunately, BMSC survival and differentiation within the host spinal cord remain poor, and these cells have been found to have various adverse effects when grafted in other pathological contexts. Moreover, paracrine-mediated actions have been proposed to explain the beneficial effects of BMSC transplantation after spinal cord injury. We thus decided to deliver BMSC-released factors to spinal cord injured rats and to study, in parallel, their properties in vitro. We show that, in vitro, BMSC-conditioned medium (BMSC-CM) protects neurons from apoptosis, activates macrophages and is pro-angiogenic. In vivo, BMSC-CM administered after spinal cord contusion improves motor recovery. Histological analysis confirms the pro-angiogenic action of BMSC-CM, as well as a tissue protection effect. Finally, the characterization of BMSC-CM by cytokine array and ELISA identified trophic factors as well as cytokines likely involved in the beneficial observed effects. In conclusion, our results support the paracrine-mediated mode of action of BMSCs and raise the possibility to develop a cell-free therapeutic approach. [less ▲]

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See detailAcetylation and Wallerian degeneration
Boerboom, Angélique ULg; Chaballe, Linda; Close, Pierre ULg et al

Poster (2012, October)

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See detailInfluence of type of contraction upon tendinous tissue during training: animal model
Kaux, Jean-François ULg; Drion, Pierre ULg; Croisier, Jean-Louis ULg et al

in Meeusen, R; Duchateau, J; Roelands, B (Eds.) et al Book of Abstracts of the 17th annual Congress of the ECSS (2012, July)

Introduction: The treatment of choice for tendinopathies is eccentric reeducation. Although the clinical results appear favourable, the biomechanical changes to the tissue are not yet clear. Materiel and ... [more ▼]

Introduction: The treatment of choice for tendinopathies is eccentric reeducation. Although the clinical results appear favourable, the biomechanical changes to the tissue are not yet clear. Materiel and methods: This study compared the effects of two methods of training (eccentric (E) training and concentric (C) training) with untrained (U) rats. The animals underwent training over a period of five weeks. The tricipital, patellar and Achilles tendons were subsequently removed to perform a traction test to the point of tendon rupture, and a histological analysis was performed. Results: There was a significant improvement in the rupture force of the patellar and tricipital tendons between the U and E groups. The tricipital tendons in the control group presented a significantly smaller cross-section than the E- and C-trained groups. No significant difference was observed for the constraints between the three groups for all three tendons. However, a tendency towards improvement was observed between the trained and the U groups for the patellar tendon. Histological studies demonstrated the development of a greater number of blood vessels and a larger quantity of collagen in the eccentric group. Discussion and conclusion: The mechanical properties of tendons in rats improve after specific training, especially following eccentric training. [less ▲]

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See detailMesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions.
Quertainmont, Renaud; Cantinieaux, Dorothée ULg; Botman, Olivier et al

in PLoS ONE (2012), 7(6), 39500

Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord ... [more ▼]

Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue. [less ▲]

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See detailInfluence sur le tissu tendino(-musculaire) du mode de contraction en entraînement : modèle animal
Kaux, Jean-François ULg; Drion, Pierre ULg; Croisier, Jean-Louis ULg et al

in Julia, Marc; Hirt, Daniel; Croisier, Jean-Louis (Eds.) et al Tendon et jonction tendino-musculaire - De la biomécanique aux applications thérapeutiques (2011)

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See detailInvolvement of placental growth factor in Wallerian degeneration
Chaballe, Linda ULg; Close, Pierre ULg; SEMPELS, Maxime ULg et al

in Glia (2011), 59(3), 379-396

Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively ... [more ▼]

Wallerian degeneration (WD) is an inflammatory process of nerve degeneration, which occurs more rapidly in the peripheral nervous system compared with the central nervous system, resulting, respectively in successful and aborted axon regeneration. In the peripheral nervous system, Schwann cells (SCs) and macrophages, under the control of a network of cytokines and chemokines, represent the main cell types involved in this process. Within this network, the role of placental growth factor (PlGF) remains totally unknown. However, properties like monocyte activation/attraction, ability to increase expression of pro-inflammatory molecules, as well as neuroprotective effects, make it a candidate likely implicated in this process. Also, nothing is described about the expression and localization of this molecule in the peripheral nervous system. To address these original questions, we decided to study PlGF expression under physiological and degenerative conditions and to explore its role in WD, using a model of sciatic nerve transection in wild-type and Pgf(-/-) mice. Our data show dynamic changes of PlGF expression, from periaxonal in normal nerve to SCs 24h postinjury, in parallel with a p65/NF-κB recruitment on Pgf promoter. After injury, SC proliferation is reduced by 30% in absence of PlGF. Macrophage invasion is significantly delayed in Pgf(-/-) mice compared with wild-type mice, which results in worse functional recovery. MCP-1 and proMMP-9 exhibit a 3-fold reduction of their relative expressions in Pgf(-/-) injured nerves, as demonstrated by cytokine array. In conclusion, this work originally describes PlGF as a novel member of the cytokine network of WD. [less ▲]

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