Increased Sensitivity of Computed Tomography Scan for Neoplastic Tissues Using the Extracellular Vesicle Formulation of the Contrast Agent Iohexol.

Computed tomography (CT) is a diagnostic medical imaging modality commonly used to detect disease and injury. Contrast agents containing iodine, such as iohexol, are frequently used in CT examinations to more clearly differentiate anatomic structures and to detect and characterize abnormalities, including tumors. However, these contrast agents do not have a specific tropism for cancer cells, so the ability to detect tumors is severely limited by the degree of vascularization of the tumor itself. Identifying delivery systems allowing enrichment of contrast agents at the tumor site would increase the sensitivity of detection of tumors and metastases, potentially in organs that are normally inaccessible to contrast agents, such as the CNS. Recent work from our laboratory has identified cancer patient-derived extracellular vesicles (PDEVs) as effective delivery vehicles for targeting diagnostic drugs to patients' tumors. Based on this premise, we explored the possibility of introducing iohexol into PDEVs for targeted delivery to neoplastic tissue. Here, we provide preclinical proof-of-principle for the tumor-targeting ability of iohexol-loaded PDEVs, which resulted in an impressive accumulation of the contrast agent selectively into the neoplastic tissue, significantly improving the ability of the contrast agent to delineate tumor boundaries.

The role of milk-derived exosomes in the treatment of diseases.

Exosomes (EXOs) are natural nanoparticles of endosome origin that are secreted by a variety of cells in the body. Exosomes have been found in bio-fluids such as urine, saliva, amniotic fluid, and ascites, among others. Milk is the only commercially available biological liquid containing EXOs. Proof that exosomes are essential for cell-to-cell communication is increasingly being reported. Studies have shown that they migrate from the cell of origin to various bioactive substances, including membrane receptors, proteins, mRNAs, microRNAs, and organelles, or they can stimulate target cells directly through interactions with receptors. Because of the presence of specific proteins, lipids, and RNAs, exosomes act in physiological and pathological conditions in vivo. Other salient features of EXOs include their long half-life in the body, no tumorigenesis, low immune response, good biocompatibility, ability to target cells through their surface biomarkers, and capacity to carry macromolecules. EXOs have been introduced to the scientific community as important, efficient, and attractive nanoparticles. They can be extracted from different sources and have the same characteristics as their parents. EXOs present in milk can be separated by size exclusion chromatography, density gradient centrifugation, or (ultra) centrifugation; however, the complex composition of milk that includes casein micelles and milk fat globules makes it necessary to take additional issues into consideration when employing the mentioned techniques with milk. As a rich source of EXOs, milk has unique properties that, in addition to its role as a carrier, promotes its use in treating diseases such as digestive problems, skin ulcers, and cancer, Moreover, EXOs derived from camel milk are reported to reduce the risk of oxidative stress and cancer. Milk-derived exosomes (MDEs) from yak milk improves gastrointestinal tract (GIT) development under hypoxic conditions. Furthermore, yak-MDEs have been suggested to be the best treatment for intestinal epithelial cells (IEC-6 cell line). Because of their availability as well as the non-invasiveness and cost-effectiveness of their preparation, isolates from mammals milk can be excellent resources for studies related to EXOs. These features also make it possible to exploit MDEs in clinical trials. The current study aimed to investigate the therapeutic applications of EXOs isolated from various milk sources.

Does survivin overexpression enhance the efficiency of fibroblast cell-based wound therapy?

Cell-based wound therapy is faced with some limiting factors that decrease the therapeutic efficacy of transplanted cells. In this study, we aimed to genetically modify fibroblast cells with anti-apoptotic Survivin gene (Birc5) before cell transplantation. In vitro, pIRES2-eGFP-Survivin plasmid was transfected into the fibroblast cells and the growth curve was evaluated for transfected and normal cells performing MTT assay. In vivo, two 6-diameter cutaneous wounds were created at mice dorsal skin. Fibrin clot was used as a delivery vehicle to transfer cells into the wound bed. The effects of four treatment groups including (a) Cell-SVV-Clot (b) Cell-GFP-Clot, (c) Normal cell-Clot and, (d) Clot alone were evaluated. After 1,2,3,7 and 14 days post-transplantation, the wounds were photographed for evaluating the wound closure rate and wound samples were obtained. Angiogenesis and formation of granulated tissue were assessed via H&E staining for wound samples. The expression levels of Survivin, VEGF, and bFGF genes were also determined using qRT-PCR. The MTT assay showed similar proliferation potential of transfected cells with normal cells verifying that Survivin had no detrimental effect. Compared to the Normal cell-Clot group, the Survivin overexpression was seen for 3 days in the Cell-SVV-Clot group verifying the cell survival during the early stage of wound healing. The Survivin further upregulated VEGF and bFGF expressions resulting in more angiogenesis and formation of granulated tissue by day 3 and 14. The treated wounds with Cell-SVV-Clot were regenerated with a higher wound closure rate by day 7 compared to Normal cell-Clot and Clot groups. Survivin enhanced wound healing through induction of VEGF and bFGF at particular times post-wounding that led to a more structured-epidermis with higher angiogenesis and granulation tissue formation rate.