Innovative Stem Cell Technique Accelerates Creation of Microglia for Brain Research and Disease Modeling

A groundbreaking approach at Harvard University has enabled the rapid and efficient generation of human microglia-like cells from induced pluripotent stem cells (iPSCs). Microglia, vital immune cells in the brain accounting for about 10% of its cells, play essential roles in neuroinflammation, clearing debris, and supporting neural circuits. Dysfunction of microglia is linked to various neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's disease, ALS, and multiple sclerosis.

Traditionally, obtaining human microglia is challenging due to the invasive biopsies required, and rodent microglia differ significantly from humans, complicating translational research. To overcome these hurdles, researchers at the Wyss Institute and Harvard Medical School led by George Church developed a novel system that reduces the differentiation process from 35 days to just four, saving time and resources.

This new method builds on the TFome™ platform, a comprehensive library of transcription factors (TFs) critical to cell fate determination. The team engineered TF libraries specific to microglia and screened different combinations to identify a potent six-TF cocktail capable of transforming iPSCs into microglia-like cells rapidly. These cells exhibited key genetic and functional similarities to primary human microglia, including responses to inflammatory stimuli and disease-related proteins like TDP-43.

Further refinement involved additional screening with a second set of TFs, resulting in a 6-TF cocktail that enhances microglia maturity and functionality. The cells demonstrated expected behavior when exposed to neuroinflammatory signals, such as interferon gamma, and pathogenic proteins associated with neurodegeneration, confirming their potential use in studying disease mechanisms.

The ability to produce microglia efficiently opens new avenues for brain disease research, drug discovery, and personalized medicine. This platform technology also holds promise for generating other difficult-to-isolate cell types, advancing the development of next-generation regenerative therapies. Overall, this innovation represents a significant step toward better understanding and treating neurological diseases.

Source: https://medicalxpress.com/news/2025-06-stem-cell-platform-aims-recreate.html