Strategies and principles for establishing a prolonged microglia-free niche to achieve meaningful and efficient microglia replacement. (IMAGE)
Caption
For the most widely used Mr BMT-based strategy, microglia are removed by pharmacological inhibition of CSF1R. And the prolonged microglia-free niche is created through conditioning by irradiation or chemotherapy.
Alternatively, excessive proliferation by multiple-round depletion-repopulation can shorten the telomere and thus impair the capacity of microglial proliferation. This regimen can also maintain a prolonged microglia-free niche.
Engineered CSF1R inhibition-resistant donor cells can be transplanted upon a prolonged microglia-free condition via continuous CSF1R inhibition.
For transgenic CX3CR1-CreER::CSF1Rfl/fl and CX3CR1-CreER::Rosa-DTA mice that can induce microglial cell death, the prolonged microglia-free niche can be maintained by continuous tamoxifen treatment without affecting the donor cells.
In addition, the CSF1RΔFIRE/ΔFIRE mice per se are in a naturally microglia-free condition.
Credit
Bo Peng et al.
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