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In addition to its essential role in normal development, angiogenesis plays a vital role in pathologies such as cancer, diabetes and atherosclerosis. Mathematical and computational modeling has contributed to unraveling its complexity. Many existing theoretical models of angiogenic sprouting are based on the \u201csnail\u2010trail\u201d hypothesis. This framework assumes that leading ECs positioned at sprout tips migrate toward low\u2010oxygen regions while other ECs in the sprout passively follow the leaders' trails and proliferate to maintain sprout integrity. However, experimental results indicate that, contrary to the snail\u2010trail assumption, ECs exchange positions within developing vessels, and the elongation of sprouts is primarily driven by directed migration of ECs. The functional role of cell rearrangements remains unclear. This review of the theoretical modeling of angiogenesis is the first to focus on the phenomenon of cell mixing during early sprouting. We start by describing the biological processes that occur during early angiogenesis, such as phenotype specification, cell rearrangements and cell interactions with the microenvironment. Next, we provide an overview of various theoretical approaches that have been employed to model angiogenesis, with particular emphasis on recent in silico models that account for the phenomenon of cell mixing. Finally, we discuss when cell mixing should be incorporated into theoretical models and what essential modeling components such models should include in order to investigate its functional role.<\/jats:p><jats:p>This article is categorized under:<jats:list list-type=\"simple\">\n<jats:list-item><jats:p>Cardiovascular Diseases &gt; Computational Models<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cancer &gt; Computational Models<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wsbm.1634","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T22:49:56Z","timestamp":1702421396000},"source":"Crossref","is-referenced-by-count":10,"title":["Computational modeling of angiogenesis: The importance of cell rearrangements during vascular 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