{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:11:30Z","timestamp":1793020290030,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0008503","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000}}],"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21AI131701"],"award-info":[{"award-number":["1R21AI131701"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Onchocerciasis also known as river blindness is a neglected tropical disease and the world's second-leading infectious cause of blindness in humans; it is caused by\n                    <jats:italic>Onchocerca volvulus<\/jats:italic>\n                    . Current treatment with ivermectin targets microfilariae and transmission and does not kill the adult parasites, which reside within subcutaneous nodules. To support the development of macrofilaricidal drugs that target the adult worm to further support the elimination of onchocerciasis, an in-depth understanding of\n                    <jats:italic>O<\/jats:italic>\n                    .\n                    <jats:italic>volvulus<\/jats:italic>\n                    biology especially the factors that support the longevity of these worms in the human host (&gt;10 years) is required. However, research is hampered by a lack of access to adult worms.\n                    <jats:italic>O<\/jats:italic>\n                    .\n                    <jats:italic>volvulus<\/jats:italic>\n                    is an obligatory human parasite and no small animal models that can propagate this parasite were successfully developed. The current optimized 2-dimensional (2-D)\n                    <jats:italic>in vitro<\/jats:italic>\n                    culturing method starting with\n                    <jats:italic>O<\/jats:italic>\n                    .\n                    <jats:italic>volvulus<\/jats:italic>\n                    infective larvae does not yet support the development of mature adult worms. To overcome these limitations, we have developed and applied 3-dimensional (3-D) culture systems with\n                    <jats:italic>O<\/jats:italic>\n                    .\n                    <jats:italic>volvulus<\/jats:italic>\n                    larvae that simulate the human\n                    <jats:italic>in vivo<\/jats:italic>\n                    niche using\n                    <jats:italic>in vitro<\/jats:italic>\n                    engineered skin and adipose tissue. Our proof of concept studies have shown that an optimized indirect co-culture of\n                    <jats:italic>in vitro<\/jats:italic>\n                    skin tissue supported a significant increase in growth of the fourth-stage larvae to the pre-adult stage with a median length of 816\u2013831 \u03bcm as compared to 767 \u03bcm of 2-D cultured larvae. Notably, when larvae were co-cultured directly with adipose tissue models, a significant improvement for larval motility and thus fitness was observed; 95% compared to 26% in the 2-D system. These promising co-culture concepts are a first step to further optimize the culturing conditions and improve the long-term development of adult worms\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Ultimately, it could provide the filarial research community with a valuable source of\n                    <jats:italic>O<\/jats:italic>\n                    .\n                    <jats:italic>volvulus<\/jats:italic>\n                    worms at various developmental stages, which may accelerate innovative unsolved biomedical inquiries into the parasite\u2019s biology.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0008503","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T13:55:44Z","timestamp":1604584544000},"page":"e0008503","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Preliminary evaluations of 3-dimensional human skin models for their ability to facilitate in vitro the long-term development of the debilitating obligatory human parasite Onchocerca volvulus"],"prefix":"10.1371","volume":"14","author":[{"given":"Christoph","family":"Malkmus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Jawahar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3895-7062","authenticated-orcid":true,"given":"Nancy","family":"Tricoche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2389-6113","authenticated-orcid":true,"given":"Sara","family":"Lustigman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4132-9737","authenticated-orcid":true,"given":"Jan","family":"Hansmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,5]]},"reference":[{"issue":"4","key":"pntd.0008503.ref001","doi-asserted-by":"crossref","first-page":"e0003664","DOI":"10.1371\/journal.pntd.0003664","article-title":"Control, 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