Human iPSC-derived microglia: A growing toolset to study the brain's innate immune cells
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Updated: Dec 31, 2025
Transplantation of Human Induced Pluripotent Stem Cell-Derived Microglia in Immunocompetent Mice Brain via Non-Invasive Transnasal Route
Published on: May 31, 2022
Jonathan Hasselmann1,2,3, Mathew Blurton-Jones1,2,3
1Department of Neurobiology and Behavior, University of California Irvine, Irvine, California.
Abstract:
Recent advances in the generation of microglia from human induced pluripotent stem cells (iPSCs) have provided exciting new approaches to examine and decipher the biology of microglia. As these techniques continue to evolve to encompass more complex in situ and in vivo paradigms, so too have they begun to yield novel scientific insight into the genetics and function of human microglia. As such, researchers now have access to a toolset comprised of three unique "flavors" of iPSC-derived microglia: in vitro microglia (iMGs), organoid microglia (oMGs), and xenotransplanted microglia (xMGs). The goal of this review is to discuss the variety of research applications that each of these techniques enables and to highlight recent discoveries that these methods have begun to uncover. By presenting the research paradigms in which each model has been successful, as well as the key benefits and limitations of each approach, it is our hope that this review will help interested researchers to incorporate these techniques into their studies, collectively advancing our understanding of human microglia biology.
Insights
Human induced pluripotent stem cells (iPSCs) enable new ways to study microglia biology. This review covers three types of iPSC-derived microglia (in vitro, organoid, and xenotransplanted) and their research applications.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Immunology
Background:
- Recent advancements in generating microglia from human induced pluripotent stem cells (iPSCs) offer novel avenues for studying microglial biology.
- These evolving techniques are providing significant insights into the genetics and function of human microglia.
- Researchers now have access to three distinct models of iPSC-derived microglia: in vitro microglia (iMGs), organoid microglia (oMGs), and xenotransplanted microglia (xMGs).
Purpose of the Study:
- To review the diverse research applications enabled by different iPSC-derived microglia models.
- To highlight recent scientific discoveries facilitated by these innovative methodologies.
- To guide researchers in selecting and implementing appropriate iPSC-derived microglia models for their studies.
Main Methods:
- Utilizing in vitro microglia (iMGs) for controlled cellular studies.
- Employing organoid microglia (oMGs) to mimic in vivo microglial environments within brain organoids.
- Leveraging xenotransplanted microglia (xMGs) for in vivo studies in animal models.
Main Results:
- iMGs, oMGs, and xMGs provide distinct advantages for investigating human microglia genetics and function.
- Each model has demonstrated success in specific research paradigms, contributing to a deeper understanding of microglial biology.
- The review outlines the key benefits and limitations associated with each iPSC-derived microglia approach.
Conclusions:
- iPSC-derived microglia models (iMGs, oMGs, xMGs) are powerful tools for advancing human microglia research.
- Understanding the applications, benefits, and limitations of each model is crucial for effective study design.
- Widespread adoption of these techniques will collectively enhance our comprehension of human microglia biology.
