Abstract: Macrophages play crucial roles in a wide range of physiological and pathological processes, including immune response and tissue homeostasis. In this study, we present a novel approach using a three-dimensional porous microscaffold (PMS) to generate a large population of induced macrophages (iMacs) from human pluripotent stem cells (hPSCs). Interestingly, PMS facilitated the formation of vascular-like hematopoietic structures resembling the early aorta-gonad-mesonephros (AGM) region during embryogenesis. Subsequently, a population of macrophages undergoing robust proliferation emerged in PMS. Multi-omics analysis identified diverse paracrine signals within the 3D microenvironment that stimulated macrophage proliferation and activated key genes associated with proliferation and self-renewal. Functional experiments demonstrated that iMacs generated in 3D PMS could serve as off-the-shelf therapeutics and effectively alleviate symptoms of drug-resistant Streptococcus pneumoniae infections, underscoring their potential for innovative cell-based therapies.
Funding Source: This work was supported by the National Key R&D Program of China Grants 2022YFA1103103 and 2023YFA1800302 and the National Natural Science Foundation of China (NSFC) Grants 32270784 and 31970819 to Jie Na.
