Engineered Human Tissue as A New Platform for Mosquito Bite-Site Biology Investigations
Author:
Seavey Corey E.1ORCID, Doshi Mona1ORCID, Panarello Andrew P.1, Felice Michael A.1, Dickerson Andrew K.2ORCID, Jewett Mollie W.3ORCID, Willenberg Bradley J.1ORCID
Affiliation:
1. Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USA 2. Department of Mechanical, Aerospace, and Biomedical Engineering, Tickle College of Engineering, University of Tennessee, Knoxville, TN 37996, USA 3. Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL 32827, USA
Abstract
Vector-borne diseases transmitted through the bites of hematophagous arthropods, such as mosquitoes, continue to be a significant threat to human health globally. Transmission of disease by biting arthropod vectors includes interactions between (1) saliva expectorated by a vector during blood meal acquisition from a human host, (2) the transmitted vector-borne pathogens, and (3) host cells present at the skin bite site. Currently, the investigation of bite-site biology is challenged by the lack of model 3D human skin tissues for in vitro analyses. To help fill this gap, we have used a tissue engineering approach to develop new stylized human dermal microvascular bed tissue approximates—complete with warm blood—built with 3D capillary alginate gel (Capgel) biomaterial scaffolds. These engineered tissues, termed a Biologic Interfacial Tissue-Engineered System (BITES), were cellularized with either human dermal fibroblasts (HDFs) or human umbilical vein endothelial cells (HUVECs). Both cell types formed tubular microvessel-like tissue structures of oriented cells (82% and 54% for HDFs and HUVECs, respectively) lining the unique Capgel parallel capillary microstructures. Female Aedes (Ae.) aegypti mosquitoes, a prototypic hematophagous biting vector arthropod, swarmed, bit, and probed blood-loaded HDF BITES microvessel bed tissues that were warmed (34–37 °C), acquiring blood meals in 151 ± 46 s on average, with some ingesting ≳4 µL or more of blood. Further, these tissue-engineered constructs could be cultured for at least three (3) days following blood meal acquisitions. Altogether, these studies serve as a powerful proof-of-concept demonstration of the innovative BITES platform and indicate its potential for the future investigation of arthropod bite-site cellular and molecular biology.
Funder
University of Central Florida, College of Medicine National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Reference71 articles.
1. WHO (2017). Global Vector Control Response 2017–2030, World Health Organization. 2. Wheeler, N.J., Heimark, Z.W., Airs, P.M., Mann, A., Bartholomay, L.C., and Zamanian, M. (2020). Genetic and functional diversification of chemosensory pathway receptors in mosquito-borne filarial nematodes. PLoS Biol., 18. 3. GBD Disease Injury Incidence and Prevalence Collaborators (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392, 1789–1858. 4. GBD DALYs and HALE Collaborators (2016). Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet, 388, 1603–1658. 5. Mosquito saliva induced cutaneous events augment Chikungunya virus replication and disease progression;Agarwal;Infect. Genet. Evol.,2016
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