We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Physio-chemical modifications to re-engineer small extracellular vesicles for targeted anticancer therapeutics delivery and imaging
Cancer theranostics developed through nanoengineering applications are essential for targeted oncologic interventions in the new era of personalized and precision medicine. Recently, small extracellular vesicles (sEVs) have emerged as an attractive nanoengineering platform for tumor-directed anticancer therapeutic delivery and imaging of malignant tumors. These natural nanoparticles have multiple advantages over synthetic nanoparticle-based delivery systems, such as intrinsic targeting ability, less immunogenicity, and a prolonged circulation time. Since the inception of sEVs as a viable replacement for liposomes (synthetic nanoparticles) as a drug delivery vehicle, many studies have attempted to further the therapeutic efficacy of sEVs.
Human Umbilical Cord Mesenchymal Stem Cell Exosomes Deliver Potent Oncolytic Reovirus to Acute Myeloid Leukemia Cells
In addition to chemotherapy, oncolytic viruses are an efficient treatment for acute myeloid leukemia (AML). Like other oncolytic viruses, the anti-tumor efficacy of reovirus when administered intravenously is reduced due to the presence of neutralizing antibodies. In this study, we evaluated the role of exosomes in human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to deliver reovirus to AML cells. We show that UC-MSCs loaded with reovirus can deliver reovirus to tumor cells without cellular contact. We further demonstrate that GW4869 inhibits the release of exosomes as well as inhibited the transfer of reovirus from UC-MSCs to tumor cells. Mechanistically, we show that exosomes derived from reovirus-infected UC-MSCs (MSCREO-EXOs) have a tumor lysis effect and transmit reovirus to tumor cells mainly through clathrin-mediated endocytosis (CME) and macropinocytosis. In addition, we demonstrate the feasibility of using MSC-derived exosomes (MSC-EXOs) as a reovirus carrier to exert an anti-tumor effect on AML cells. Collectively, our data indicate that UC-MSCs transfer reovirus to AML cells via exosome release and prompt further study of MSC-EXOs as a potential reovirus carrier to treat AML.
Circulating tumor cells reveal early predictors of disease progression in patients with stage III NSCLC undergoing chemoradiation and immunotherapy
Circulating tumor cells (CTCs) are early signs of metastasis and can be used to monitor disease progression well before radiological detection by imaging. Using an ultrasensitive graphene oxide microfluidic chip nanotechnology built with graphene oxide sheets, we were able to demonstrate that CTCs can be specifically isolated and molecularly characterized to predict future progression in patients with stage III non-small cell lung cancer (NSCLC). We analyzed CTCs from 26 patients at six time points throughout the treatment course of chemoradiation followed by immune checkpoint inhibitor immunotherapy. We observed that CTCs decreased significantly during treatment, where a larger decrease in CTCs predicted a significantly longer progression-free survival time. Durvalumab-treated patients who have future progression were observed to have sustained higher programmed death ligand 1+ CTCs compared to stable patients. Gene expression profiling revealed phenotypically aggressive CTCs during chemoradiation. By using emerging innovative bioengineering approaches, we successfully show that CTCs are potential biomarkers to monitor and predict patient outcomes in patients with stage III NSCLC.
Exosomes as a Treatment for Skin Aging
Much of the communication that takes place between cells takes the form of secretion and uptake of extracellular vesicles, small membrane-wrapped packages of diverse molecules. Vesicles are currently categorized by size, for lack of a better taxonomy, and exosomes are one of the better studied size classes. It appears to be the case that much of the benefit of first generation stem cell therapies is produced by the signaling generated by transplanted cells, and thus the research community has started to focus on the logistically easier approach of harvesting and using extracellular vesicles rather than transplanting the cells themselves. While extracellular vesicle therapies are readily available via medical tourism, widespread use in the more regulated end of the medical community remains a work in progress.