Restoration versus reconstruction: how cell anatomy and extra-cellular matrix influence tissue regeneration

Tissue regeneration replaces damaged cells and is involved in tissue remodeling. In order to investigate the existence of a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of epidermis, neurons and skeletal muscle, characterized by different types of histological and functional organization. Following damage, all the tissues here analyzed go through three phases: inflammation, regeneration and maturation. Another common feature is the occurrence of cellular de-differentiation and/or differentiation events, including gene transcription, which are typical of embryonic development. Nonetheless, various strategies are used by different tissues to replace their lost parts. The epidermis regenerates ex novo, whereas neurons restore their missing parts; muscle fibers use a mixed strategy, based on the regrowth of missing parts through reconstruction by means of newborn fibers. The choice of either strategy is influenced by the physical, chemical and structural features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration. Taking skeletal muscle as a model, we present evidence about the importance of the fiber niche to direct and favour tissue regeneration, a phenomenon of particular relevance for highly hierarchized tissues such as striated muscles. Niche properties are accounted for by cell-cell contacts, cell-matrix interaction and paracrine effects in skeletal muscle. The ordered sequence of steps that characterizes the regeneration processes, shared by several tissues, suggests it may be possible to model this extremely important phenomenon to improve guided in situ regeneration interventions

Pathologies related to abnormal deposits in dermatology : a physico-chemical approach

Although numerous pathologies are associated with abnormal skin deposits, these remain poorly described, as accurate characterization continues to present a challenge for dermatologists. Their submicrometer size as well as their diverse chemistry require various characterization tools. We aim to exemplify characterization of endogenous and exogenous skin deposits in some selected skin diseases using different physico-chemical techniques. We begin with a presentation of selected dis-eases associated with skin deposits. We then present those of our results which show their variety of structure, location and chemical composition, obtained with various tools: Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy, X-ray fluorescence, vibra-tional spectroscopies, as well as techniques specific to synchrotron radiation. Our results constitute a real opportunity to improve diagnosis, and to understand the pathogenesis of many skin diseases, and opportunities for therapeutic intervention.Peer reviewe

Can the centrosome be a marker for DNA ploidy in breast cancer?

Background: The role of DNA ploidy in genomic instability of cancer cells and prognosis has been described in a number of studies. The role of the centrosome in cell cycle has also been reported. Aim: In this study, we aimed to investigate the correlation between the centrosome and DNA ploidy in breast cancer in a search for a cytologic predictive and prognostic marker. Materials and Methods: Cell prints were prepared from cell culture of mesothelial cells, fibroblast cell line MRC5 and breast cancer cell lines MCF7 and T47D. Indirect immunofluorescence was used with anti-γ-tubulin and centrosomes were quantified using a fluorescence microscope. DNA ploidy was scored with the DNA index analyzed by flow cytometry. Results: The normal mesothelial cells (94% of the cells with one detected centrosome) and MRC5 diploid cells (68% with two centrosomes) were used as quality controls. A correlation between the number of centrosomes and DNA ploidy was found in MCF7 cell lines (64% of the cells with a number of centrosomes ≥ 3). It was not observed in invasive breast cancer samples; however, the frequency of cells with centrosomes ≥ 3 was found to be slightly higher in DNA aneuploid samples than in DNA diploid samples (15% vs 13.3%). Conclusion: Quantification of centrosome appears to be correlated to DNA ploidy in breast cancer cell lines and slightly associated to DNA aneuploidy in invasive breast cancer. Studies analyzing a larger number of samples as well as morphological abnormalities of the centrosome are needed

Comparison between computerised lung SPECT-CT and noncontrast thoracic HRCT for quantitative analysis of post-acute COVID-19 pulmonary vascular pruning

International audienceComputerised processing of images from routine noncontrast HRCT could be an efficient, costless and safe tool to investigate the vascular remodelling that occurs in the months after COVID-19 in a large number of patients https://bit.ly/3qAQZDW

Estimation of regional pulmonary compliance in idiopathic pulmonary fibrosis based on personalized lung poromechanical modeling

International audiencePulmonary function is tightly linked to the lung mechanical behavior, especially large deforma-tion during breathing. Interstitial lung diseases, such as Idiopathic Pulmonary Fibrosis (IPF), havean impact on the pulmonary mechanics and consequently alter lung function. However, IPF re-mains poorly understood, poorly diagnosed and poorly treated. Currently, the mechanical impactof such diseases is assessed by pressure-volume curves, giving only global information. We de-veloped a poromechanical model of the lung that can be personalized to a patient based on routineclinical data. The personalization pipeline uses clinical data, mainly CT-images at two time stepsand involves the formulation of an inverse problem to estimate regional compliances. The estima-tion problem can be formulated both in terms of “effective”, i.e., without considering the mixtureporosity, or “rescaled”, i.e., where the first-order effect of the porosity has been taken into account,compliances. Regional compliances are estimated for one control subject and three IPF patients,allowing to quantify the IPF-induced tissue stiffening. This personalized model could be used in theclinic as an objective and quantitative tool for IPF diagnosis

Sleep Apnea in Idiopathic Pulmonary Fibrosis: A Molecular Investigation in an Experimental Model of Fibrosis and Intermittent Hypoxia

International audienceBackground: High prevalence of obstructive sleep apnea (OSA) is reported in incident and prevalent forms of idiopathic pulmonary fibrosis (IPF). We previously reported that Intermittent Hypoxia (IH), the major pathogenic element of OSA, worsens experimental lung fibrosis. Our objective was to investigate the molecular mechanisms involved. Methods: Impact of IH was evaluated on C57BL/6J mice developing lung fibrosis after intratracheal instillation of Bleomycin (BLM). Mice were Pre-exposed 14 days to IH before induction of lung fibrosis or Co-challenged with IH and BLM for 14 days. Weight loss and survival were daily monitored. After experimentations, lungs were sampled for histology, and protein and RNA were extracted. Results: Co-challenge or Pre-exposure of IH and BLM induced weight loss, increased tissue injury and collagen deposition, and pro-fibrotic markers. Major worsening effects of IH exposure on lung fibrosis were observed when mice were Pre-exposed to IH before developing lung fibrosis with a strong increase in sXBP1 and ATF6N ER stress markers. Conclusion: Our results showed that IH exacerbates BLM-induced lung fibrosis more markedly when IH precedes lung fibrosis induction, and that this is associated with an enhancement of ER stress markers

A New Model of Acute Exacerbation of Experimental Pulmonary Fibrosis in Mice

Rationale: idiopathic pulmonary fibrosis (IPF) is the most severe form of fibrosing interstitial lung disease, characterized by progressive respiratory failure leading to death. IPF’s natural history is heterogeneous, and its progression unpredictable. Most patients develop a progressive decline of respiratory function over years; some remain stable, but others present a fast-respiratory deterioration without identifiable cause, classified as acute exacerbation (AE). Objectives: to develop and characterize an experimental mice model of lung fibrosis AE, mimicking IPF-AE at the functional, histopathological, cellular and molecular levels. Methods: we established in C57BL/6 male mice a chronic pulmonary fibrosis using a repetitive low-dose bleomycin (BLM) intratracheal (IT) instillation regimen (four instillations of BLM every 2 weeks), followed by two IT instillations of a simple or double-dose BLM challenge to induce AE. Clinical follow-up and histological and molecular analyses were done for fibrotic and inflammatory lung remodeling analysis. Measurements and main results: as compared with a low-dose BLM regimen, this AE model induced a late burst of animal mortality, worsened lung fibrosis and remodeling, and superadded histopathological features as observed in humans IPF-AE. This was associated with stronger inflammation, increased macrophage infiltration of lung tissue and increased levels of pro-inflammatory cytokines in lung homogenates. Finally, it induced in the remodeled lung a diffuse expression of hypoxia-inducible factor 1α, a hallmark of tissular hypoxia response and a major player in the progression of IPF. Conclusion: this new model is a promising model of AE in chronic pulmonary fibrosis that could be relevant to mimic IPF-AE in preclinical trials

Laser spectroscopy for in situ elemental imaging of lung tissue: a promising technology

International audienc