Induced pluripotent stem cell-derived macrophages as a platform for modelling human disease

Area of Science:

• Immunology
• Stem Cell Biology
• Pathogenesis Research

Background:

• Macrophages are crucial innate immune cells involved in tissue homeostasis and disease.
• Dysregulation of macrophage function is linked to numerous human diseases.
• Induced pluripotent stem cells (iPSCs) provide a renewable source for generating specific cell types.

Purpose of the Study:

• To review the application of iPSC-derived macrophages (iMacs) in modeling human diseases.
• To highlight advancements in understanding macrophage roles in health and pathology through iMacs.
• To discuss the potential of iMacs for developing novel therapeutic strategies.

Main Methods:

• Generation of iPSCs from patient-derived cells or healthy donors.
• Introduction of disease-related mutations into iPSCs using CRISPR-Cas9.
• Differentiation of iPSCs into macrophages (iMacs).
• Co-culture of iMacs in 2D systems with other iPSC-derived cells or in 3D organoid models.

Main Results:

• iMacs provide unlimited access to genotype-specific cells for disease modeling.
• In vitro studies using iMacs elucidate disease etiology related to macrophage dysfunction.
• Co-culture systems enhance the physiological relevance of iMac-based disease models.

Conclusions:

• iMacs represent a revolutionary tool in macrophage biology and disease research.
• Modeling human diseases with iMacs significantly advances knowledge of macrophage function in health and disease.
• iMacs hold promise for the development of targeted therapies for diseases involving macrophage dysregulation.