Microtubule-associated protein 1B: a neuronal binding partner for myelin-associated glycoprotein

Myelin-associated glycoprotein (MAG) is expressed in periaxonal membranes of myelinating glia where it is believed to function in glia–axon interactions by binding to a component of the axolemma. Experiments involving Western blot overlay and coimmunoprecipitation demonstrated that MAG binds to a phosphorylated neuronal isoform of microtubule-associated protein 1B (MAP1B) expressed in dorsal root ganglion neurons (DRGNs) and axolemma-enriched fractions from myelinated axons of brain, but not to the isoform of MAP1B expressed by glial cells. The expression of some MAP1B as a neuronal plasma membrane glycoprotein (Tanner, S.L., R. Franzen, H. Jaffe, and R.H. Quarles. 2000. J. Neurochem. 75:553–562.), further documented here by its immunostaining without cell permeabilization, is consistent with it being a binding partner for MAG on the axonal surface. Binding sites for a MAG-Fc chimera on DRGNs colocalized with MAP1B on neuronal varicosities, and MAG and MAP1B also colocalized in the periaxonal region of myelinated axons. In addition, expression of the phosphorylated isoform of MAP1B was increased significantly when DRGNs were cocultured with MAG-transfected COS cells. The interaction of MAG with MAP1B is relevant to the known role of MAG in affecting the cytoskeletal structure and stability of myelinated axons

Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

Background: In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs) are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results: The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b) are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP) could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion: The present study highlights the existence of an inter-donor variability of expression of neuralrelated markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as well as contributing to the ongoing controversy about differentiation capacities of MSCs. Therefore, further studies need to consider the differences between donor samples prior to any treatment as well as the possibility of harvesting donor cells that may be inappropriate for transplantation strategies

Influence of type of contraction upon tendinous tissue during training: animal model

peer reviewedIntroduction: 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

Influence du mode de contraction sur le tendon : modèle animal

peer reviewedIntroduction : Les tendinopathies sont fréquentes et touchent aussi bien les membres supérieurs que les membres inférieurs. La rééducation excentrique constitue une thérapeutique de choix dans le traitement des tendinopathies. Malgré les résultats favorables en clinique, les effets morphologiques et biochimiques n’ont pas encore été élucidés. Matériel et méthodes : Dix-huit rats de souche Sprague-Dawley adultes ont été répartis en trois groupes : 6 témoins (groupe T) qui ne sont soumis à aucune contrainte physique ; 6 soumis à un effort concentrique (groupe C), course en montée ; 6 soumis à un effort excentrique (groupe E), course en descente. Les 12 rats des groupes C et E ont dû courir sur un tapis roulant incliné à +15° (groupe C) ou -15° (groupe E) à une vitesse de 17m/min (1km/h) pendant une heure à raison de trois séances par semaine pendant 5 semaines. Au terme de l’entraînement, les tendons achilléens, rotuliens et tricipitaux ont été prélevés bilatéralement. Les tendons de cinq rats de chaque groupe ont bénéficié d’une évaluation biomécanique (test de traction à l’aide de mors type « cryo-jaws »). Les tendons du sixième rat de chaque groupe ont permis l’étude histologique (coloration à l’hématoxyline-éosine et trichrome de Masson). Résultats : Le groupe E présente une augmentation de la tension de rupture des tendons rotuliens (29 ,5% ; p=0,047) et tricipitaux (72% ; p=0,018), une amélioration du rapport Force/Masse pour le tendon tricipital (54% ; p=0,043) ainsi qu’une augmentation de la section tendineuse tricipitale (74% ; p=0,008). Aucune variation pour aucun des tendons entre les groupes n’est relevée pour le paramètre contrainte (=Force/Section). Histologiquement, les tendons du groupe E se caractérisent par une plus grande quantité de vaisseaux sanguins périphériques ainsi qu’une plus grande proportion de collagène. Conclusion : Cette étude démontre que les propriétés mécaniques du tendon sont améliorées après un entraînement excentrique. Le tendon plus résistant augmente sa quantité de collagène et probablement les interactions entre les fibres de collagène

Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions

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

The spinal cord ependymal region: A stem cell niche in the caudal central nervous system

peer reviewedIn the brain, specific signalling pathways localized in highly organized regions called niches, allow the persistence of a pool of stem and progenitor cells that generate new neurons and glial cells in adulthood. Much less is known on the spinal cord central canal niche where a sustained adult neurogenesis is not observed. Here we review our current knowledge of this caudal niche in normal and pathological situations. Far from being a simple layer of homogenous cells, this region is composed of several cell types localized at specific locations, expressing characteristic markers and with different morphologies and functions. We further report on a screen of online geneexpression databases to better define this spinal cord niche. Several genes were found to be preferentially expressed within or around the central canal region (Bmp6, CXCR4, Gdf10, Fzd3, Mdk, Nrtn, Rbp1, Shh, Sox4, Wnt7a) some of which by specific cellular subtypes. In depth characterization of the spinal cord niche constitutes a framework to make the most out of this endogenous cell pool in spinal cord disorders