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Biomedical subjects

Nicolas Caron

Publications and source records attributed to Nicolas Caron.

4 recordsLinked to original sources

Decidualization and maintenance of a functional prostaglandin system in human endometrial cell lines following transformation with SV40 large T antigen.

Prostaglandins (PGs) are key regulators of reproductive function and associated pathologies. We have established stable endometrial stromal and epithelial cell lines with SV40 large T antigen (TAG) as a model to study PG action in the human endometrium. Two clones for each cell type were selected for rapid growth, PG production and response to interleukin-1beta (IL-1beta). The resulting stromal (HIESC) and epithelial (HIEEC) cells retain their characteristics for at least 40 population doublings (PDs). The selected clones express progesterone (PR) and estrogen receptor-alpha (ER-alpha) at both mRNA and protein levels. By contrast, with the existing known human endometrial cell lines Ishikawa and KLE, HIESC and HIEEC increase their production of PGF2alpha and PGE2 and cyclooxygenase (COX)-2 protein expression in response to IL-1beta. The latter cells also express the main biosynthetic enzymes involved in PG production, cytosolic phospholipase A2 (PLA2), COX-1 and COX-2, PGF synthase and PGE synthase and the corresponding EP2, EP3, EP4 and FP receptors. The selective COX-2 inhibitor NS-398 completely inhibits the increased production of PGs induced by IL-1beta in both cell types, whereas dexamethasone (DEX) exerts a stronger inhibition in HIESC than in HIEEC. The latter observation may be related to the higher expression of COX-1 measured in HIEEC. On the basis of the present characterization and previous determination of corresponding primary cell cultures, HIESC and HIEEC appear appropriate to study the contribution of PGs in the regulation of human endometrium function and associated pathologies.

Adult↗

Nanoengineered liquid mirrors shaped by thermal fields.

We discuss a new type of deformable mirror made from nanoengineered reflective layers deposited onto liquids. The surfaces are shaped by heating with a laser. The response times of the deformed surfaces are slow (> 1 s). Simplicity and low cost appear to be the main advantages of thermally deformable liquid mirrors.

Journal Article↗

Dynamics of the early immune cellular reactions after myogenic cell transplantation.

The role of immune cells in the early donor cell death/survival following myoblast transplantation is confusing, one of the reasons being the lack of data about the immune reactions following cell transplantation. We used outbred mice as hosts for transplantation of primary cultured muscle cells and T-antigen-immortalized myoblasts. The host muscles were analyzed 1 h to 7 days after cell injection. No net loss of the donor primary cultured cell population was observed in this period. The immune cellular reaction in this case was: 1) a brief (<48 h) neutrophil invasion; 2) macrophage infiltration from days 1 to 7; 3) a specific response involving CTL and few NK cells (days 6 and 7), preceded by a low CD4+ cell infiltration starting at day 3. In contrast, donor-immortalized myoblasts completely disappeared during the 7-day follow-up. In this case, an intense infiltration of CTL and macrophages, with moderate CD4+ infiltration and lower amounts of NK cells, was observed starting at day 2. The nonspecific immune response at days 0 and 1 was similar for both types of donor cells. The present observations set a basis to interpret the role of immune cells on the early death/survival of donor cells following myoblast transplantation.

Animals↗

Autotransplantation in mdx mice of mdx myoblasts genetically corrected by an HSV-1 amplicon vector.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder, characterized by a lack of dystrophin. To eliminate the need for immunosuppressive drugs, transplantation of genetically modified autologous myoblasts has been proposed as a possible therapy for this myopathy. An HSV-1 amplicon vector (HSVDGN), containing a 17.3-kb full-length MCK-driven mouse dystrophin cDNA, an eGFP gene, and a neomycin resistance gene driven by CMV or SV40 promoters, respectively, was constructed and used to transduce mdx primary myoblasts. The presence of the eGFP and neomycin resistance genes facilitated the evaluation of the initial transduction efficiency and the permanent transduction frequency. At low multiplicities of infection (MOI 1-5), the majority of myoblasts (60-90%) expressed GFP. The GFP-positive mdx myoblasts were sorted by FACS and selected with neomycin (300 microg/ml) for 2 weeks. Up to 2% of initially infected mdx myoblasts stably expressed the three transgenes without further selection at that time. These altered cells were grafted into the tibialis anterior muscles of 18 mdx mice. Some of the mice were immunosuppressed with FK506 due to the anticipation that eGFP and the product of neomycin resistance gene might be immunogenic. One month after transplantation, numerous muscle fibers expressing mouse dystrophin were detected by immunohistochemistry, in both immunosuppressed (10-50%) and nonimmunosuppressed (5-25%) mdx mice. Our results demonstrated the capability of permanently expressing a full-length dystrophin in dystrophic myoblasts with HSV-1 amplicon vector and raised the possibility of an eventual treatment of DMD based on the transplantation of genetically modified autologous myoblasts.

Animals↗