# Microglia-associated progression of multiple sclerosis: target identification and therapeutic engagement in human in vitro models

## TL;DR

This paper reviews how human in vitro models, especially those involving microglia, can help understand and treat multiple sclerosis.

## Contribution

The paper provides a critical review of using human-induced pluripotent stem cell-derived models to study microglia's role in MS progression.

## Key findings

- Human in vitro models, including organoids, can simulate MS progression more accurately than traditional methods.
- Induced pluripotent stem cell-derived microglia offer new insights into MS mechanisms and potential therapies.

## Abstract

Chronic progression of multiple sclerosis (MS) is likely to develop on the basis of a highly complex interaction of different mechanisms, which are probably already present at disease onset. While animal models have been instrumental in developing therapies for relapsing forms of MS, they have provided limited insight into the processes driving disease progression. To overcome these limitations, human in vitro models have emerged as powerful tools to dissect cellular mechanisms and identify novel therapeutic targets. Here, we highlight advances in modeling MS progression, using human induced pluripotent stem cell-derived systems, with a particular focus on microglia as key mediators of neuroinflammation and neurodegeneration. We critically discuss the strengths and limitations of current induced pluripotent stem cell-based microglia models, and their utility in target identification and therapeutic engagement. By emphasizing translational applications and methodological innovations, this Review provides a framework for leveraging human in vitro models to better understand and therapeutically modulate microglia-associated progression in MS.

Multiple sclerosis (MS) is a disease affecting the central nervous system, leading to inflammation and nerve damage. This Review explores new ways to study MS progression using lab-grown cells. Researchers use in vitro models to mimic human brain cells, including microglia. These models range from simple cell cultures to complex three-dimensional structures called organoids. Organoids can simulate brain environments more accurately, helping scientists understand how MS progresses. The study highlights the potential of using human induced pluripotent stem cells, which can turn into any cell type, including microglia. These induced pluripotent stem cell-derived models offer insights into MS mechanisms and help test new treatments. The findings suggest that, while no model perfectly replicates MS, these advanced techniques provide valuable tools for research.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.