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Although chemotherapy may enrich CSCs through selection or by inducing dedifferentiation, the dynamic changes in the tumor niche and their impact on CSCs during chemotherapy remain unclear. In this study, single\u2010cell sequencing and multiplex immunohistochemical analysis are used to define microenvironmental changes, and a post\u2010chemotherapy increase in efferocytotic macrophages that phagocytosed chemotherapy\u2010induced apoptotic tumor cells is identified. Efferocytotic macrophages are associated with poor prognosis and CSCs in OC. Their conditioned medium facilitates OC stemness in vitro. Meanwhile, targeting efferocytosis suppresses CSC enrichment, chemoresistance, and regrowth in vivo. Mechanistically, it is demonstrated that enhanced expression of ODC1 driven by efferocytosis increases polyamine flux, particularly putrescine, by integrating metabolomics and transcriptomics. The increase in putrescine content leads to the\n                    <jats:italic>SPP1<\/jats:italic>\n                    and OPN overexpression in macrophages, conferring cancer stemness to OC cells through the OPN\u2010CD44 axis. Treatment with an ODC1 selector inhibitor mitigates CSC enrichment, sensitizes tumors to cisplatin, and restricts tumor regrowth. Together, the study shows that efferocytosis and associated polyamine metabolic reprogramming support the chemotherapy\u2010induced enrichment of CSCs, providing new targets for addressing chemoresistance and recurrence of OC.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512508","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T02:53:31Z","timestamp":1763780011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efferocytosis\u2010Driven Polyamine Metabolism in Macrophages Enhances Cancer Stem Cell Enrichment after Chemotherapy in Ovarian Cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3296-0711","authenticated-orcid":false,"given":"Wenhan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Union Hospital Tongji Medical College Huazhong University of Science and Technology  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