Biology subjects

Weiss, D. J.

Publications and source records attributed to Weiss, D. J..

7 recordsLinked to original sources

bioRxiv2026

Recreating the Native Airway Microenvironment Using Tissue-Specific Extracellular Matrix Bioinks for Proximal Airway Engineering

Ex vivo airway engineering approaches such as 3D bioprinting offer a promising strategy for generating functional airway replacements, but the fabrication of hollow, patient-specific proximal airway constructs using translationally relevant bioinks remains challenging. This study describes the development of biocompatible, polymer-blended human airway-derived decellularized extracellular matrix (AW-dECM) bioinks for engineering structurally and mechanically relevant airway tissues. An optimal formulation consisting of 30 mg/mL AW-dECM and nanofibrillar cellulose alginate conjugated to RGD supported the bioprinting of simple and complex hollow airway structures with mechanical properties comparable to native airways ([~]8-10 kPa). The bioinks also promoted primary human airway epithelial cell viability, adhesion, and differentiation into mucociliary and secretory phenotypes during 28 days of air-liquid interface culture. Furthermore, subcutaneous implantation in immunocompetent rats demonstrated excellent biodegradative stability and overall biocompatibility over 30 days. Collectively, these findings establish a foundation for improved physiological airway models and future tissue-engineered airway replacements.

bioengineering↗

bioRxiv2025

Let-7b-5p loaded Mesenchymal Stromal Cell Extracellular Vesicles reduce Pseudomonas- biofilm formation and inflammation in CF Bronchial Epithelial Cells

Cystic Fibrosis (CF) is a multiorgan disease caused by mutations in the CFTR gene, leading to chronic pulmonary infections and hyperinflammation. Among pathogens colonizing the CF lung, Pseudomonas aeruginosa is predominant, infecting over 50% of adults with CF, and becoming antibiotic-resistant over time. Current therapies for CF, while providing tremendous benefits, fail to eliminate persistent bacterial infections, chronic inflammation, and irreversible lung damage, necessitating novel therapeutic strategies. Our group engineered mesenchymal stromal cell derived extracellular vesicles (MSC EVs) to carry the microRNA let-7b-5p as a dual anti-infective and anti-inflammatory treatment. MSC EVs are low-immunogenicity platforms with innate antimicrobial and immunomodulatory properties, while let-7b-5p reduces biofilm formation and inflammation. In a preclinical CF mice model, we reported that let-7b-5p-loaded MSC EVs reduced P. aeruginosa burden, immune cells, and proinflammatory cytokines in the lungs. We hypothesize four complementary mechanisms for the observed in-vivo effects of the let-7b-5p loaded MSC EVs: antimicrobial activity, anti-inflammatory properties, inhibition of antibiotic-resistant P. aeruginosa biofilm formation in CF airways, and stimulation of anti-inflammatory macrophage behaviors. This study focused on the second and third mechanisms and demonstrates that MSC EVs engineered to contain let-7b-5p effectively blocked the formation of antibiotic-resistant P. aeruginosa biofilms on primary human bronchial epithelial cells (pHBECs) while also reducing P. aeruginosa-induced inflammation. This approach holds promise for improving outcomes for people with CF. Future work will focus on optimizing delivery strategies and expanding the clinical applicability of MSC EVs to target other CF-associated pathogens. NEW AND NOTEWORTHYThis is the first study demonstrating that let-7b-5p loaded Mesenchymal Stromal Cell Extracellular Vesicles (MSC EVs) block antibiotic-resistant P. aeruginosa biofilm formation and reduce inflammation in CF primary human bronchial epithelial cells. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/656674v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@3754b3org.highwire.dtl.DTLVardef@99dadcorg.highwire.dtl.DTLVardef@efc4b3org.highwire.dtl.DTLVardef@15aed48_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Extracellular Vesicles Derived from Mesenchymal Stromal Cells Reduce Pseudomonas aeruginosa Lung Infection and Inflammation in Mice

The World Health Organization and the U.S. Centers for Disease Control and Prevention have reported that antibiotic resistant infections with Pseudomonas aeruginosa present a significant health risk world-wide. In the genetic disease Cystic Fibrosis (CF), chronic antibiotic resistant Pseudomonas lung infections and persistent inflammation remain the leading causes of mortality. While highly effective modulator therapy (HEMT) dramatically improves lung function in CF, they fail to eradicate chronic infections or eliminate the associated hyperinflammatory state. Thus, there is an urgent need for innovative therapies that can simultaneously eliminate antibiotic resistant P. aeruginosa lung infection and the attendant hyperinflammatory lung environment. Mesenchymal stromal cell-derived extracellular particles (MSC EPs) represent a promising solution, offering potent anti-inflammatory and antimicrobial properties while being safe and non-toxic. This study demonstrates using a CF mouse model of infection that MSC EPs reduce acute P. aeruginosa lung infection and inflammation. As the first investigation of MSC EPs in CF mice, this research underscores the dual effects of MSC EPs; reducing inflammation and bacterial burden. These findings mark an important advancement in antimicrobial therapy, addressing the unmet need for reducing antibiotic resistant infections and hyperinflammation in CF as well as other diseases with chronic, antibiotic resistant P. aeruginosa infections.

microbiology↗

bioRxiv2024

Development of a Multifunctional Extracorporeal Life Support (ECLS) System for Lung and Kidney Support: The Pneuma-K ECLS System

Multi-organ failure (MOF), particularly in the coexistence of acute kidney injury (AKI) and acute lung injury (ALI), presents a significant challenge in intensive care units (ICU) and is associated with exceedingly high mortality rates. Respiratory and renal failures are frequently managed by extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), respectively. However, employing these therapies using separate devices requires specialized facilities, adds to complexity, and increases the risks of clotting due to the extensive artificial surface areas involved. Therefore, an integrated device capable of providing simultaneous respiratory and renal support is essential. This paper introduces the Pneuma-K ECLS system, which incorporates a multifunctional detoxifying filter (MDF) capable of performing gas exchange and renal replacement in a single cartridge. Ex-vivo blood tests confirmed the ability of the MDF to oxygenate blood, remove carbon dioxide, and eliminate uremic toxins. In addition, animal experiments demonstrated the considerable clinical potential of this novel integrated extracorporeal life support approach. Integrating respiratory and renal support into a singular device could mitigate risks, conserve resources, and enhance the survival rates of critically ill patients suffering from concurrent lung and kidney failure.

bioengineering↗

bioRxiv2020

Modelling the impact of climate change on the distribution and abundance of tsetse in Northern Zimbabwe

Background Climate change is predicted to impact the transmission dynamics of vector-borne diseases. Tsetse flies (Glossina) transmit species of Trypanosoma that cause human and animal African trypanosomiasis. A previous modelling study showed that temperature increases between 1990 and 2017 can explain the observed decline in abundance of tsetse at a single site in the Mana Pools National Park of Zimbabwe. Here, we apply a mechanistic model of tsetse population dynamics to predict how increases in temperature may have changed the distribution and relative abundance of Glossina pallidipes across northern Zimbabwe.Methods Local weather station temperature measurements were previously used to fit the mechanistic model to longitudinal G. pallidipes catch data. To extend the use of the model, we converted MODIS land surface temperature to air temperature, compared the converted temperatures with available weather station data to confirm they aligned, and then re-fitted the mechanistic model using G. pallidipes catch data and air temperature estimates. We projected this fitted model across northern Zimbabwe, using simulations at a 1 km × 1 km spatial resolution, between 2000 to 2016.Results We produce estimates of relative changes in G. pallidipes mortality, larviposition, emergence rates and abundance, for northern Zimbabwe. Our model predicts decreasing tsetse populations within low elevation areas in response to increasing temperature trends during 2000-2016. Conversely, we show that high elevation areas (>1000 M.A.S.L), previously considered too cold to sustain tsetse, may now be climatically suitable.Conclusions The results of this research represent the first regional-scale assessment of temperature related tsetse population dynamics, and the first high spatial-resolution estimates of this metric for northern Zimbabwe. Our results suggest that tsetse abundance may have declined across much of the Zambezi valley in response to changing climatic conditions during the study period. Future research including empirical studies is planned to improve model accuracy and validate predictions for other field sites in Zimbabwe.Competing Interest StatementThe authors have declared no competing interest.View Full Text

ecology↗

bioRxiv2018

The origins and relatedness structure of mixed infections vary with local prevalence of P. falciparum malaria

Individual malaria infections can carry multiple strains of Plasmodium falciparum with varying levels of relatedness. Yet, how local epidemiology affects the properties of such mixed infections remains unclear. Here, we develop an enhanced method for strain deconvolution from genome sequencing data, which estimates the number of strains, their proportions, identity-by-descent (IBD) profiles and individual haplotypes. Applying it to the Pf3k data set, we find that the rate of mixed infection varies from 29% to 63% across countries and that 51% of mixed infections involve more than two strains. Further-more, we estimate that 47% of symptomatic dual infections contain sibling strains likely to have been co-transmitted from a single mosquito, and find evidence of mixed infections propagated over successive infection cycles. Finally, leveraging data from the Malaria Atlas Project, we find that prevalence correlates within Africa, but not Asia, with both the rate of mixed infection and the level of IBD.

epidemiology↗

bioRxiv2018

Genomic and epidemiological monitoring of yellow fever virus transmission potential

The yellow fever virus (YFV) epidemic that began in Dec 2016 in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes sp. vectors highlights the urgent need to monitor the risk of re-establishment of domestic YFV transmission in the Americas. We use a suite of epidemiological, spatial and genomic approaches to characterize YFV transmission. We show that the age- and sex-distribution of human cases in Brazil is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally using a new protocol reveals an early phase of sylvatic YFV transmission restricted to Minas Gerais, followed in late 2016 by a rise in viral spillover to humans, and the southwards spatial expansion of the epidemic towards previously YFV-free areas. Our results establish a framework for monitoring YFV transmission in real-time, contributing to the global strategy of eliminating future yellow fever epidemics.

epidemiology↗