{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:26:06Z","timestamp":1785547566885,"version":"3.56.0"},"reference-count":81,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T00:00:00Z","timestamp":1646179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C24\/18\/085"],"award-info":[{"award-number":["C24\/18\/085"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The process of granuloma formation is complex, and due to species differences, the validity of animal studies is somewhat questioned. Moreover, the large number of animals needed to observe the different stages of development also raises ethical questions. Therefore, researchers have explored the use of human peripheral blood mononuclear cells (PBMCs), a heterogeneous population of immune cells, in an in vitro model. This review included in vitro studies that focused on exposing PBMCs\u2014from healthy, sensitized, or diseased individuals\u2014to antigens derived from infectious agents\u2014such as mycobacteria or Schistosoma spp.\u2014or inorganic antigens\u2014such as beryllium. The reviewed studies mainly explored how human in vitro granuloma models can contribute towards understanding the pathogenesis of granulomatous diseases, especially during the early stages of granuloma formation. The feasibility of granuloma modelling was thus largely assessed via experimental techniques including (1) granuloma scoring indices (GI), (2) cell surface markers and (3) cytokine secretion profiling. While granuloma scoring showed some similarities between studies, a large variability of culture conditions and endpoints measured have been identified. The lack of any standardization currently impedes the success of a human in vitro granuloma model.<\/jats:p>","DOI":"10.3390\/cells11050864","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T08:37:16Z","timestamp":1646210236000},"page":"864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Assessment of Experimental Techniques That Facilitate Human Granuloma Formation in an In Vitro System: A Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2499-1083","authenticated-orcid":false,"given":"Nirosha","family":"Ganesan","sequence":"first","affiliation":[{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, 3001 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-2691","authenticated-orcid":false,"given":"Steven","family":"Ronsmans","sequence":"additional","affiliation":[{"name":"Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3001 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-3518","authenticated-orcid":false,"given":"Jeroen","family":"Vanoirbeek","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, 3001 Leuven, Belgium"},{"name":"Centre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, 3001 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0292-6603","authenticated-orcid":false,"given":"Peter H. 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