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Updated: Jan 11, 2026
Transplantation of Human Induced Pluripotent Stem Cell-Derived Microglia in Immunocompetent Mice Brain via Non-Invasive Transnasal Route
Published on: May 31, 2022
CSF1R inhibitor-resistant model for CNS-wide microglia replacement strategies
Jean Paul Chadarevian1, Jasmine Nguyen2, Lauren Le3
1Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Researchers developed a new mouse model for less-invasive microglia replacement therapy. This model enables effective engraftment of donor cells, advancing treatments for neurological disorders.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Cell-based therapies show promise but face challenges in treating neurological disorders.
- Current microglial replacement strategies often require invasive methods and yield cells distinct from native microglia.
Purpose of the Study:
- To develop a less-invasive microglia replacement strategy that preserves microglial ontogeny.
- To create a mouse model for assessing CSF1R inhibitor (CSF1Ri)-resistant microglia replacement.
Main Methods:
- Developed a Csf1r-G793A knockin mouse model.
- Administered CSF1Ri-resistant murine and induced pluripotent stem cell (iPSC)-derived human microglia via intracisternal delivery.
- Assessed microglial densities and peripheral hematopoietic populations.
Main Results:
- G793A mice exhibited normal microglial densities and peripheral hematopoietic populations.
- These mice demonstrated broad CSF1Ri resistance, enabling microglia replacement via intraparenchymal injection or bone marrow transplantation.
- Widespread microglia replacement was achieved through less-invasive intracisternal delivery of resistant microglia.
Conclusions:
- The Csf1r-G793A knockin mouse is a robust model for preclinical investigation of microglia replacement strategies.
- This model supports less-invasive approaches for neurological disorder treatments.
- It facilitates the use of both murine and human iPSC-derived microglia for transplantation.
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