Cell therapy for bone fracture repair: A comparative preclinical review of mesenchymal stromal cells from bone marrow and from adipose tissue

Over the last decade, there has been an increasing interest among researchers for human mesenchymal stromal cells (MSC). Their regenerative properties, multilineage differentiation capacity and immunomodulatory properties make them promising candidates for treatment in various conditions. Emerging biotechnology companies specialized in cellular and regenerative therapies have been focusing their interest on MSC-based therapies, and their use in clinical trials has steadily increased. Notably, MSC are currently tested in clinical trials addressing unmet medical needs in the field of bone fracture repair and more specifically in non-union and delayed union fractures where the bone repair process is impaired. Although MSC can be isolated from various tissues, the most commonly studied sources are bone marrow (BM) and adipose tissue (Ad). In this article, we reviewed the literature directly comparing BM- and Ad-MSC for their in vitro characteristics and in vivo osteogenic potential to determine which source of MSC would be more appropriate for bone fracture repair. As considerable variations in experimental settings between studies were found, our review was based on studies meeting specific sets of criteria, notably regarding donors’ age and gender. This review of side-by-side comparisons suggests that while BM-and Ad-MSC share common general characteristics, BM-MSC have a higher intrinsic osteogenic capacity in vitro and bone repair potential in vivo

Co-ordination of cell cycle and differentiation in the developing nervous system

During embryonic development, cells must divide to produce appropriate numbers, but later must exit the cell cycle to allow differentiation. How these processes of proliferation and differentiation are co-ordinated during embryonic development has been poorly understood until recently. However, a number of studies have now given an insight into how the cell cycle machinery, including cyclins, CDKs (cyclin-dependent kinases), CDK inhibitors and other cell cycle regulators directly influence mechanisms that control cell fate and differentiation. Conversely, examples are emerging of transcriptional regulators that are better known for their role in driving the differentiated phenotype, which also play complementary roles in controlling cell cycle progression. The present review will summarise our current understanding of the mechanisms co-ordinating the cell cycle and differentiation in the developing nervous system, where these links have been, perhaps, most extensively studied

Expression des sulfhydryl oxydases QSOX et ALR dans le système nerveux central et les organes périphériques de rat

Les sulfhydryl oxydases représentent une famille émergeante d'enzymes dont le rôle est de catalyser, dans des peptides et des protéines, l'oxydation des groupements sulfhydryls en ponts disulfures. Des études récentes menées in vitro ont montré qu'elles sont impliquées dans des mécanismes moléculaires et cellulaires essentiels, tels que le repliement des protéines, le contrôle du cycle cellulaire et la signalisation de l'apoptose. Cependant, peu de travaux ont été entrepris concernant leur distribution fine dans les différents tissus de l'organisme. Ainsi, afin d'approfondir les connaissances sur leur(s) rôle(s) biologique(s), nous avons étudié, dans le système nerveux central et les organes périphériques de rat, à l'aide de techniques de biologie moléculaire et histologiques, l'expression de deux protéines appartenant à des sous-familles distinctes de sulfhydryl oxydases associées au FAD [flavine adénine nucléotide] : la quiescine/sulfhydryl oxydase QSOX et la protéine ALR (augmenter of liver regeneration)Sulfhydryl oxidases represent an emerging family of enzymes which catalyze the oxidation of sulfhydryl groups into disulfide bonds in peptides and proteins. Recent in vitro studies showed that they are involved in essential molecular and cellular mechanisms such as protein folding, control of the cell cycle and apoptosis signalling. However, few works have described their precise distribution in the different tissues of the organism. ln the present work, the expression of two proteins belonging to distinct subfamilies of FAD-linked sulfhydryl oxidases, QSOX (quiescin/sulfhydryl oxidase) and ALR (augmenter of liver regeneration), were studied in the central nervous system and peripheral organs of the rat, using biomolecular and histological approachesBESANCON-BU Médecine pharmacie (250562102) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Cell-specific localization of the sulphydryl oxidase QSOX in rat peripheral tissues.

International audienceRat quiescin/sulphydryl oxidase (rQSOX) introduces disulphide bridges into peptides and proteins with the reduction of molecular oxygen to hydrogen peroxide. Its occurrence has been previously highlighted in a wide range of organs by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analyses, methods that have provided information concerning its expression in whole organs but that do not reveal the cell types expressing this enzyme. In this report, in addition to RT-PCR and Western blot experiments, the cell-specific localization of rQSOX has been investigated in a wide range of male and female adult rat tissues by using in situ hybridization and immunohistochemistry. Labelling was detected in most organs and systems including the immune, endocrine and reproductive systems, the respiratory, digestive and urinary tracts and the skin. No labelling was observed in the heart, blood vessel endothelium, liver or smooth and skeletal muscles. rQSOX expression was mainly localized in epithelial cells specialized in secretion, strengthening the hypothesis that QSOX enzymes play an important role in the mechanism of secretion, notably in the folding of secreted proteins. The intracellular patterns of immunolabelling indicate that the protein usually follows the secretory pathway, which is in accordance with its secreted nature and its presumed involvement in the elaboration of the extracellular matrix. In seminiferous tubules, where a high level of expression was noticed, QSOX might play an important physiological role in sperm function and serve as a marker for the diagnosis of male infertility