Highly cohesive dual nanoassemblies for complementary multiscale bioimaging

International audienceInnovative nanostructures made of a high payload of fluorophores and superparamagnetic nanoparticles (NPs) have simply been fabricated upon self-assembling in a two-step process. The resulting hybrid supraparticles displayed a dense shell of iron oxide nanoparticles tightly attached through an appropriate polyelectrolyte to a highly emissive non-doped nanocore made of more than 10 5 small organic molecules. Cooperative magnetic dipole interactions arose due to the closely packed magnetic NPs at the nanoarchitecture surface, causing enhanced NMR transverse relaxivity. Large in vivo MRI T 2 contrast was thus obtained with unusually diluted solutions after intravenous injection in small rodents. Two-photon excited fluorescence imaging could be performed, achieving unprecedented location resolution for agents combining both magnetic nanoparticles and fluorescence properties. Finally, TEM imaging of the sectioned mouse tissue succeeded in isolating the core–shell structures, which represents the first image of intact complex magnetic and fluorescent nanoassemblies upon in vivo injection. Such highly cohesive dual nanoarchitectures should open great horizons toward the assessment with high spatial resolution of the drug or labeled stem cell biodistribution

Autologous fat grafting: A comparative study of four current commercial protocols

International audienceBackground: Autologous fat grafting is a widely used technique that gives natural results when treating soft tissue deficiencies. However, there is no consensus on which is the best procedure to use, leading to unpredictable results because of fat graft resorption.Objectives: This study compared four commercial lipotransfer devices by analyzing the behavior of the processed adipose tissue and outcome of the adipose graft in an in vivo model.Methods: Four different protocols that used manual, power-assisted or water-assisted lipoas-piration and then decantation, centrifugation, or filtration were used on each of eight patients to process lipoaspirate. Harvested adipose tissue was assessed in vitro for tissue resorption, oil formation, and cytokine secretion. Graft resorption rate was calculated and histological analyses were performed after subcutaneously injecting the harvested adipose tissue in a murine model. Results: All protocols resulted in very low oil formation and histologically healthy grafts. The tissue volume was significantly greater after 2 days in culture when using manual lipoaspiration and soft centrifugations/washing steps (Microfill® /Macrofill®) compared to Water-Assisted Li-poaspiration/Decantation (BodyJet®) and Power-Assisted Lipoaspiration/Filtration (PAL® + PureGraft®). These results were confirmed in mice 1 month after subcutaneous injection , with greater efficiency obtained with protocols that used (A) manual aspiration, (B) soft centrifugations, and (C) washing steps

Evaluation of intracavitary administration of curcumin for the treatment of sarcomatoid mesothelioma

International audienceA rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration. The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro. Secondly, the potential of intraperitoneal curcumin administration to kill tumor cells in vivo was evaluated in tumor-bearing rats, in comparison with a reference epigenetic drug, SAHA. Both agents administered at days 21 and 26 after tumor challenge produced necrosis within the solid tumors at day 28. However, tumor tissue necrosis induced with curcumin was much more extensive than with SAHA, and was characterized by infiltration with mononuclear phagocytic cells. In contrast, tumor tissue treated with SAHA contained foci of resistant cells and was infiltrated by many isolated CD8+ cells. The treatment of tumor-bearing rats with 1.5 mg/kg curcumin on days 7, 9, 11 and 14 after tumor challenge dramatically reduced the mean total tumor mass at day 16. Clusters of CD8+ T lymphocytes were observed at the periphery of small residual tumor masses in the peritoneal cavity, which presented a significant reduction in mitotic index, IL6 and vimentin expression compared with tumors in untreated rats. These data open up interesting new prospects for the therapy of sarcomatoid mesothelioma with curcumin and its derivatives

Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors

International audienceGlioblastoma multiforme (GBM) represents the most frequent and deadliest primary brain tumor.Aggressive treatment still fails to eliminate deep brain infiltrative and highly resistant tumor cells.Human Vg9Vd2 T cells, the major peripheral blood gd T cell subset, react against a wide array oftumor cells and represent attractive immune effector T cells for the design of antitumor therapies.This study aims at providing a preclinical rationale for immunotherapies in GBM based on stereotaxicadministration of allogeneic human Vg9Vd2 T cells. The feasibility and the antitumor efficacy ofstereotaxic Vg9Vd2 T cell injections have been investigated in orthotopic GBM mice model usingselected heterogeneous and invasive primary human GBM cells. Allogeneic human Vg9Vd2 T cellssurvive and patrol for several days within the brain parenchyma following adoptive transfer and cansuccessfully eliminate infiltrative GBM primary cells. These striking observations pave the way foroptimized stereotaxic antitumor immunotherapies targeting human allogeneic Vg9Vd2 T cells in GBMpatients

Characterization of preneoplastic and neoplastic rat mesothelial cell lines: the involvement of TETs, DNMTs, and 5-hydroxymethylcytosine

International audienceMalignant mesothelioma (MM) is one of the worst cancers in terms of clinical outcome, urging the need to establish and characterize new preclinical tools for investigation of the tumorigenic process, improvement of early diagnosis and evaluation of new therapeutic strategies. For these purposes, we characterized a collection of 27 cell lines established from F344 rats, after 136 to 415 days of induction with crocidolite asbestos administered intraperitoneally. Four mesotheliomas were distinguished from 23 preneoplastic mesothelial cell lines (PN) according to their propensity to generate tumors after orthotopic transplantation into syngeneic rats, their growth pattern, and the expression profile of three genes. PN cell lines were further discriminated into groups / subgroups according to morphology in culture and the expression profiles of 14 additional genes. This approach was completed by analysis of positive and negative immunohistochemical MM markers in the four tumors, of karyotype alterations in the most aggressive MM cell line in comparison with a PN epithelioid cell line, and of human normal mesothelial and mesothelioma cells and a tissue array. Our results showed that both the rat and human MM cell lines shared in common a dramatic decrease in the relative expression of Cdkn2a and of epigenetic regulators, in comparison with PN and normal human mesothelial cells, respectively. In particular, we identified the involvement of the relative expression of the Ten-Eleven Translocation (TET) family of dioxygenases and Dnmt3a in relation to the 5-hydroxymethylcytosine level in malignant transformation and the acquisition of metastatic potential. INTRODUCTION Malignant mesothelioma (MM) is a rare, aggressive cancer mainly related to asbestos exposure [1], the long latency time between exposure and occurrence of clinical symptoms limiting the efficacy of therapeutic interventions. Given its chemoresistance, current therapies have a negligible impact on overall survival due to a lack of understanding of the complex biology of MM [2]. Thus, a better understanding of the different steps in the development of this disease should be of great interest for the identification of early markers of MM AU