Biology subjects

Jewell, C.

Publications and source records attributed to Jewell, C..

5 recordsLinked to original sources

bioRxiv2025

Bacterial extracellular vesicles as a tunable platform for vaginal drug delivery

There is a critical gap in the development of new therapeutic platforms designed to treat gynecologic and obstetric diseases. Compared to systemic drug delivery, vaginal drug administration of nanoparticle formulations limits off-target side effects while increasing therapeutic concentration in target tissues, showing promise for clinical translation. However, these formulations suffer from limited scalability, high-cost reagents, and long optimization timelines. Recent work highlights the potential of bacterial extracellular vesicles (bEVs) as a low-cost, tunable platform for therapeutic applications. Here, we evaluate bEVs as a therapeutic carrier for vaginal drug delivery. We demonstrate the loading of the model protein moxNeonGreen into Escherichia coli Nissle 1917 bEVs. By optimizing growth parameters, we increase protein loading into bEVs. We evaluate the effect of bEVs on the vaginal microenvironment, and observe no negative impact on vaginal epithelial cells, endocervical cells, or vaginal bacteria in vitro. Additionally, we observe the retention of bEVs in the murine female reproductive tract for more than six hours. This study provides a framework for using genetically engineered bEVs to rapidly generate customizable therapies for a range of gynecologic and obstetric conditions, addressing longstanding challenges in womens health therapeutics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=50 SRC="FIGDIR/small/658669v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@e483d2org.highwire.dtl.DTLVardef@8a6d2corg.highwire.dtl.DTLVardef@5756borg.highwire.dtl.DTLVardef@5fdb67_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Modeling Immunosenescence on-a-chip: a platform for cancer vaccine efficacy assessment

Immunosenescence dramatically reduces cancer vaccine efficacy in elderly patients, who represent the majority of cancer cases. Despite this clinical reality, age-related immune decline is rarely considered in preclinical testing. Therefore, novel in vitro models to test cancer vaccine efficacy, considering immunosenescence, are needed. Our novel lymph node paracortex on-a-chip (LNPoC) platform addresses this gap by recapitulating age-dependent immune responses against cancer vaccines, specifically antigen presentation, antigen-specific T cell activation, and antitumoral responses. Using this platform, we demonstrated that bone marrow-derived antigen-presenting cells (APCs) from young mice (6-7 weeks) displayed significantly enhanced ovalbumin (OVA) peptide presentation compared to APCs from older mice (35-36 weeks). This age-dependent difference translated to significantly greater OVA-specific CD8+ T cell activation and increased cytotoxicity against B16-OVA cancer cells. These age-dependent differences are unique to our LNPoC and undetectable in traditional 2D cultures, confirming that our LNPoC was more effective than 2D cultures at recapitulating immunosenescence-mediated immune responses against cancer vaccines in vitro. The in vivo validation confirms these findings, as young mice demonstrated higher OVA-specific CD8+ T cell responses and smaller tumors than older mice. Our LNPoC is a valuable tool for assessing immunosenescences impact on cancer vaccines, potentially guiding more effective therapies for older adults.

bioengineering↗

bioRxiv2024

Microphysiological system modeling pericyte-induced temozolomide resistance in glioblastoma

Glioblastoma (GBM) is a malignancy with poor survival and high rates of chemoresistance. Temozolomide (TMZ), the standard-of-care chemotherapy for GBM patients, but GBM cells can be resistant to TMZ, resulting in limited clinical efficacy. Elucidating the complex mechanisms of TMZ chemoresistance in GBM requires novel in vitro models replicating the complex tumor microenvironment (TME). We present an multicellular 3D GBM model recapitulating the biomechanical characteristics of brain tissues and pericyte-mediated TMZ resistance. The composite hydrogel used to encapsulate GBM spheroids (U87, LN229, and PDM140), pericytes, or GBM spheroids with pericytes, mimics the rheological properties of brain tissues (G[~]800Pa and G"[~]100Pa). When untreated, the GBM models remain viable and proliferative for 14 days. PDM140 spheroids were most sensitive to TMZ (IC50=73M), followed by LN229 (IC50=278M) and U87 (IC50=446M). With pericytes, the viability of TMZ-treated GBM spheroids significantly increases by 22.7% for PDM140, 32.5% for LN229, and 22.1% for U87, confirming pericyte-induced GBM chemoresistance responses. The upregulation (380-fold) of C-C motif chemokine ligand 5 (CCL5) in pericytes upon TMZ treatment could explain the chemoresistance responses. This innovative brain-mimicking 3D GBM model represents a novel in vitro platform for testing the efficacy of TMZ and novel drugs targeting CCL5-mediated chemoresistance pathways in GBM.

bioengineering↗

bioRxiv2023

Household geckos as a potential vector for Salmonella transmission in Malawi

Salmonella was isolated from 23/79 (29.1%) gecko stool samples from households in southern Malawi. Whole genome sequencing of 47 isolates revealed 27 Salmonella serovars spanning two subspecies. Our results demonstrate that geckos play an important role in the carriage and potentially, transmission of Salmonella within households.

ecology↗

bioRxiv2022

Emerging variants of canine enteric coronavirus associated with seasonal outbreaks of severe canine gastroenteric disease

Canine enteric coronavirus (CECoV) variants have an emerging role in severe outbreaks of canine gastroenteritis. Here we used syndromic health data from a sentinel network of UK veterinary practices to identify an outbreak of severe canine gastroenteritis. Affected dogs frequently presented with vomiting, diarrhoea and inappetence. Data from sentinel diagnostic laboratories showed similar seasonal increases in CECoV diagnosis. Membrane glycoprotein (M) gene sequence analysis implied wide geographical circulation of a new CECoV variant. Whole genome sequencing suggested the main circulating 2022 variant was most closely related to one previously identified in 2020 with additional spike gene recombination; all variants were unrelated to CECoV-like viruses recently associated with human respiratory disease. Identifying factors that drive population-level evolution, and its implications for host protection and virulence, will be important to understand the emerging role of CECoV variants in canine and human health, and may act as a model for coronavirus population adaptation more widely.

genomics↗