Biomedical subjects

Véronique Moulin

Publications and source records attributed to Véronique Moulin.

6 recordsLinked to original sources

PubMed2004

Tissue-engineered human asthmatic bronchial equivalents.

The isolation of human bronchial epithelial (HBEC) and fibroblastic cells (HBFC) from biopsies of asthmatic and non-asthmatic volunteers provided unique cellular materials to be used for the production of bioengineered bronchial equivalents (BE) in vitro. The HBEC are grown on a mesenchymal layer seeded with HBFC and the BE can be maintained for at least 15 days in culture. Under the BE culture conditions established previously, HBEC undergo differentiation into ciliated and goblet cells, within a pseudostratified organization comparable to human bronchi. We published previously the results from histologic and functional analyses of such BE produced exclusively using non-asthmatic HBEC and HBFC. We report here the comparative analyses of BE produced with non-asthmatic and asthmatic living HBEC and HBFC (naBE and aBE, respectively). Our data indicated that all asthmatic HBEC populations grown on a mesenchymal layer, containing non-asthmatic HBFC, slowly reached a confluent state but then detached from the matrix upon culture time. These BE appear to be very good models to study the mechanisms involved in asthma in vitro.

Adult↗

PubMed2004

Normal skin wound and hypertrophic scar myofibroblasts have differential responses to apoptotic inductors.

During wound healing, myofibroblasts play a central role in matrix formation and wound contraction. At the end of healing, there is evidence that myofibroblasts disappear via apoptotic pathways. Hypertrophic scars are a fibroproliferative disorder that leads to considerable morbidity. It has been postulated that a defect in myofibroblast apoptosis could be responsible for the pathological scar formation, but no evidence exists. We have isolated and cultured human normal wound (Wmyo) and hypertrophic scar (Hmyo) myofibroblasts and compared their basal apoptotic rates and their sensitivity to serum starvation and Fas antibody-induced apoptosis to that obtained for dermal fibroblasts (Fb). A higher rate of apoptosis as evidenced by morphological criteria and a propidium iodide assay was observed for Wmyo in comparison to Fb and Hmyo. These results came along with a low level of the anti-apoptotic proteins Bcl-2 and Bclx(L) in Wmyo, whereas there was an increase in the level of the pro-apoptotic molecule Bax when compared to the results obtained for Fb and Hmyo. Hmyo showed a higher level of Bcl-2 compared to Fb but no difference in the Bax or Bclx(L) level. After serum starvation, Wmyo revealed an increased apoptotic rate, whereas Hmyo and Fb did not show any difference. Anti-Fas treatment did not modify the levels of apoptosis but strongly increased the cell growth of Hmyo as compared to Wmyo. This is the first study presenting a broad vision of the apoptotic sensitivity of normal and pathological myofibroblasts. These results confirmed the hypothesis of defects in apoptosis and growth during pathological scar formation impeding myofibroblast disappearance at the end of healing.

Actins↗

PubMed2004

Sensitivity of myofibroblasts to H2O2-mediated apoptosis and their antioxidant cell network.

During wound healing, the transition from granulation to scar tissue shows a decrease in myofibroblast cellularity. Previous results have correlated the disappearance of these cells with the induction of apoptotic cell death by some unknown stimuli. In contrast, hypertrophic scar appearance after wound healing is thought to be linked to a disorder of apoptotic function which induces myofibroblast persistence in granulation tissue. Oxidative stress being an important mediator of apoptosis, we have evaluated the apoptotic response of normal and pathological wound myofibroblasts (WMyo and HMyo respectively) in their interaction with two oxidative stress inducers: hydrogen peroxide, using a high concentration as a single dose, and sodium ascorbate which induced a continuous release of H2O2 at a low concentration. Our results showed that, according to the H2O2 treatment type, HMyo were more sensitive (after ascorbate treatment) or less sensitive (after H2O2 treatment) when compared to WMyo and Fb. We next assessed the presence of several molecules known to be involved in the antioxidant network protecting cells against H2O2 injury and found HMyo to have a higher level of activity of glutathione peroxidase and a lower level of activity of catalase than WMyo. These results can help explain the contradictory responses of myofibroblasts according to the oxidative stress treatment. This is the first study linking refractory oxidative stress mediated cell death to cellular phenotype in hypertrophic myofibroblasts, and indicates a pivotal role for the antioxidant enzyme system in this type of resistance.

Adult↗

PubMed2004

Tissue-engineered skin substitutes: from in vitro constructs to in vivo applications.

The field of skin tissue engineering is a paradigm for the various efforts towards the reconstruction of other tissues and organ substitutes. As skin replacement, this biotechnological approach has evolved from simple cultured autologous epidermal sheets to more complex bilayered cutaneous substitutes. The various types of such substitutes are herein presented with their intended use. However, two integrative characteristics are analysed more specifically because of their critical role: neovascularization and re-innervation. Furthermore, the in vitro use of these various skin substitutes has shed light on various physiological and pathological phenomena. Thus, not only the in vivo application of these skin substitutes as grafts, but also their in vitro value as skin models, are presented.

Animals↗

PubMed2003

[Tissue engineering: a tool to understand the physiological mechanisms].

Tissue engineering is a new domain, which allows some very unique studies of many human physiological mechanisms. This technology, based on cell capacity to reproduce a three-dimensional tissue with or without the help of biomaterials, is an interesting approach to study cells in an environment quite similar to the in vivo context. This article summarizes the LOEX's (laboratory of experimental organogenesis) scientific endeavor in tissue engineering in order to better understand some physiological or pathological mechanisms. Thus wound healing, stem cells, graft vascularization and cell interactions are domains where tissue engineering has already made a significant impact.

Cell Communication↗

PubMed2002

CD40 triggering increases the efficiency of dendritic cells for antitumoral immunization.

Recent studies have shown the importance of triggering CD40 molecules to enhance the efficiency of dendritic cells (DCs) as antigen-presenting cells (APCs). The P198 and P1A tumor antigens, which are expressed by mastocytoma P815, have been assessed for their immunogenicity using different modes of immunization. We measured CTL responses induced in vivo with antigenic peptides P198 and P1A loaded onto bone marrow-derived DCs that had matured as a consequence of CD40-CD40L interactions. CD40L-transfected 3T3 fibroblasts were used as a source of CD40L signal. Our results show that this mode of DC activation considerably improves their ability to induce CTLs against P198 and P1A antigens in vivo as compared to untreated DCs. We also show that immunizations carried out with CD40L-activated DCs loaded with the P1A peptide induce a very efficient protection against a lethal challenge with P815 tumor cells, which express P1A. Our results indicate that the efficiency of DC-based vaccines used in clinical trials of cancer immunotherapy could be increased significantly by triggering DCs via CD40 prior to immunization.

3T3 Cells↗