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Updated: Feb 26, 2026
Production and Characterization of Human Macrophages from Pluripotent Stem Cells
Published on: April 16, 2020
Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident
Kazuyuki Takata1, Tatsuya Kozaki2, Christopher Zhe Wei Lee2
1Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore; Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Abstract:
Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.
Insights
Induced pluripotent stem cells (iPSCs) can generate primitive macrophage precursors (iMacs). These iMacs can differentiate into specialized tissue-resident macrophages, including microglia and alveolar macrophages, offering new avenues for research and therapy.
Area of Science:
- Stem cell biology
- Immunology
- Developmental biology
Background:
- Tissue macrophages originate from embryonic yolk-sac progenitors.
- Previous limitations in isolating yolk-sac-derived macrophages hindered research.
- Induced pluripotent stem cells (iPSCs) offer a potential in vitro model for studying early hematopoiesis.
Purpose of the Study:
- To investigate the differentiation potential of iPSC-derived primitive macrophages (iMacs).
- To determine if iMacs can mature into specialized, tissue-resident macrophages.
- To explore the utility of iMacs in modeling diseases and for therapeutic applications.
Main Methods:
- Directed differentiation of human and murine iPSCs into iMacs.
- Co-culture of iMacs with iPSC-derived neurons to induce microglial differentiation.
- In vivo differentiation of murine iMacs following transplantation into the brain and lung.
- Generation of iMacs from iPSCs of a familial Mediterranean fever patient.
Main Results:
- iPSC-derived neurons promoted the differentiation of iMacs into microglia-like cells in vitro.
- In vivo studies showed iMacs differentiating into functional microglia in the brain and alveolar macrophages in the lung.
- Patient-derived iMacs exhibited pro-inflammatory characteristics, mirroring familial Mediterranean fever phenotypes.
Conclusions:
- iMacs serve as a valuable source of tissue-resident macrophage precursors.
- This iPSC-based system facilitates biological, pathophysiological, and therapeutic studies of macrophages.
- The findings open possibilities for regenerative medicine and disease modeling using patient-specific iPSCs.
