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Despite recent advances in gene therapy and stem cell transplantation, treatment options remain very limited, highlighting the urgent need for the development of new therapeutic approaches. Human erythroid model systems of SCD represent emerging tools for the discovery of disease\u2010modifying strategies through drug screening and mechanistic studies. This review describes the range of models available, including patient\u2010derived red blood cells, hematopoietic stem cells, induced pluripotent stem cells, and immortalized cell lines, and summarizes their relative advantages and disadvantages, as well as potential integration with more complex integrated co\u2010culture and organoid models. Overall, these cellular systems represent an expanding toolkit available to SCD researchers with the potential to reduce reliance on the use of animal models.<\/jats:p>","DOI":"10.1002\/hem3.70488","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:18:13Z","timestamp":1792077493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human erythroid models of sickle cell disease"],"prefix":"10.1002","volume":"10","author":[{"given":"Deborah E.","family":"Daniels","sequence":"first","affiliation":[{"name":"School of Biochemistry University of Bristol Bristol United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9836-4164","authenticated-orcid":false,"given":"Maria A.","family":"Lizarralde\u2010Iragorri","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Mechanisms of Hematological Disorders and 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