Efficient generation of human dendritic cells from iPSC by introducing a feeder-free expansion step for hematopoietic progenitors
Efficient generation of human dendritic cells from iPSC by introducing a feeder-free expansion step for hematopoietic progenitors
Abstract Dendritic cells (DCs) are rare innate immune cells that are essential regulators of anti-tumour, anti-viral and vaccine responses by the adaptive immune system. Conventional dendritic cells, particularly the cDC1 subset, are most desired for DC-based immunotherapies, however, it can be difficult to isolate sufficient numbers of primary cells from patients. The most common alternate sources of DC are ex vivo, such as monocyte-derived or DC expanded from cord blood hematopoietic progenitors. Induced pluripotent stem cells (iPSC) offer a promising solution, providing an opportunity for in vitro generating DCs that are suitable for patient-derived or off-the-shelf batch-manufactured cells. Here, we developed an in vitro protocol designed to maximise the yield of iPSC-derived DC progenitors, with the specific goal of generating DC1-like cells. The iPSC-DCs subsets generated by our method could be partitioned by cell surface phenotypes of cDC1, cDC2 and DC3, but they were most transcriptionally similar to monocyte-derived DC (MoDC). Stimulated iPSC-DCs generated pro-inflammatory cytokines, expressed migratory chemokine receptors including CCR7 which indicates capacity to traffic through lymphatic endothelium, and upregulated co-stimulatory molecules, indicating their potential for productive interactions with T-cells. This method offers a promising step towards an expandable source of allogeneic human dendritic cells for future applications.
Butcher Suzanne K、Mintern Justine D、Wells Christine A、Sakkas Magdaline、Radford Kristen J、Elahi Zahra、Jameson Vanta
Stem Cell Systems, Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of MelbourneDepartment of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of MelbourneStem Cell Systems, Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of MelbourneMelbourne Cytometry Platform, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of MelbourneMater Research Institute, The University of Queensland, Translational Research InstituteStem Cell Systems, Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of MelbourneMelbourne Cytometry Platform, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne
基础医学生物科学研究方法、生物科学研究技术细胞生物学
Dendritic CellcDCMoDChematopoietic progenitorinduced pluripotent stem celliPSC
Butcher Suzanne K,Mintern Justine D,Wells Christine A,Sakkas Magdaline,Radford Kristen J,Elahi Zahra,Jameson Vanta.Efficient generation of human dendritic cells from iPSC by introducing a feeder-free expansion step for hematopoietic progenitors[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2024.06.04.594010.点此复制
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