# Accelerating Functional Maturation of Human iPSC-Derived Microglia

> **NIH NIH R43** · BRAINXELL, INC. · 2021 · $255,217

## Abstract

Project Summary/Abstract
 Neurological and psychiatric disorders, including Alzheimer’s disease (AD), exert a devastating personal
and economic toll on patients, families, caregivers, and society. This is in part due to our failure to develop
effective medications, reflecting drug discovery platforms that are often not relevant to target diseases. The
recent development of induced pluripotent stem cells (iPSCs) from humans makes it possible to screen and
validate candidate compounds on human brain cells, including those from patients, thus potentially increasing
the success rate and speeding the pace of CNS drug development.
 BrainXell, Inc. has pioneered the development of human patient brain cell-based platforms for CNS drug
discovery. We are able to produce large quantities of highly enriched microglia of consistent quality from human
iPSCs through our platform technology of directed differentiation and expansion of committed progenitors.
However, iPSC-derived microglia are immature, comparable to those at the fetal stage, which makes it difficult
for presentation of disease phenotypes and for high-throughput screening (HTS) for drug leads intended for
those whose brains are fully mature. The goal of this Phase I SBIR project is to uncover molecules that speed
the expression of genes associated with a mature state in iPSC-derived microglia and to formulate cocktails that
yield mature microglia within 1-3 weeks after plating. We will engineer a human iPSC reporter line with
nanoluciferase (Nluc) fused to P2RY12, a purinergic receptor highly expressed in mature microglia. This line will
enable and simplify the screening of small molecules for accelerating microglia maturation. Formulation of an
effective cocktail for rapidly generating mature human microglia will remove a major roadblock in establishing
human patient microglia-based HTS for CNS drug development.

## Key facts

- **NIH application ID:** 10259242
- **Project number:** 1R43AG073055-01
- **Recipient organization:** BRAINXELL, INC.
- **Principal Investigator:** Zhong-wei Du
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $255,217
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10259242

## Citation

> US National Institutes of Health, RePORTER application 10259242, Accelerating Functional Maturation of Human iPSC-Derived Microglia (1R43AG073055-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10259242. Licensed CC0.

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