We have established a syngeneic mouse brain tumor model in which tumor growth or disappearance can be easily monitored using bioluminescence imaging. We have successfully treated tumors with microglia obtained from neonatal animals as proof of principle that a microglial treatment strategy may be effective. On average, treated groups achieve a long term survival rate of 60%-70% whereas control animals routinely achieve a 0% long term survival rate. We have created iPS cell lines from mice syngeneic to those implanted with tumors and have fully characterized their multipotency using teratoma formation and blastocyst injections. We have developed a protocol for differentiating the iPS cells into microglia and have confirmed their microglial identity. The resulting iPS-derived microglia are as effective as neonatal microglia in prolonging the survival of brain tumor bearing mice. In related work, we have also developed a protocol for the differentiation of human iPSC into microglia. We believe that the human protocol will be valuable for studying the to role of microglia in human neurological diseases and also potentially for the treatment of selected diseases.
