First step towards cell therapy for brain diseases - University of Freiburg

First steps towards cell therapy for brain diseases

Researchers in Freiburg found a way to selectively replace defective immune cells in the brain in animal models. This is an important first step in cell therapy for Alzheimer's and other brain diseases. The findings were published in the journal Nature Immunology.

Artist's impression of brain border areas from dura mater to parenchyma, showing clusters of resident macrophages (blue) and infiltrating monocyte-derived macrophages (yellow).Image: Freiburg University Hospital / Maximilian Flygoff

The brain and its connections are controlled by special immune cells.Researchers at the Faculty of Medicine of the University of Freiburg have now studied the phagocytes in the meninges and blood of the brain, which control the removal of waste from the brain and the inflammatory process.Scientists at the Institute of Neuropathology at the University of Freiburg, together with an international team of researchers, have shown that the control of cell death occurs through the administration of drugs.As a result, it is changed especially in the new cells that come and thus affect their work.In the future, this method may be the basis of a new treatment to combat vascular damage in Alzheimer's disease.The research published in the journal Nature Immunology was done on genetic mice lines.The information obtained is an important building block for the use of genetic therapy for brain diseases in the future.

"In our method, we can choose to replace the phagocyte, also known as macrophages, in the brain tissue. The macrophages inside the brain, found directly in the brain cells, are not changed," said the head of the research Prof. of Freiburg."The tested cells are part of the blood-brain barrier, which makes medical access that we can replace macrophages for the first time now. a great development," added Dr.Lukas Amann, head of the group at the Institute of Neuropathology at the University Hospital Freiburg and last author of the study.

The brain can be divided into two areas, border zones and functional tissues.In both, macrophages are the dominant immune cell type.Macrophages at brain interfaces sit directly on the blood-brain barrier formed by cerebral blood vessels.There, they control what substances enter the brain, thereby protecting it from harmful substances, sediments, and pathogens.At the same time, brain waste is also removed through the blood vessels, with macrophages playing an important regulatory role.

Prof. Dr. Marco Prinz, Medical Director, Institute of Neuropathology at the University of Freiburg Hospital. Photo: CIBSS University, Freiburg

Importance for Alzheimer's, etc.

Brain waste is very important to remove brain waste because it is very harmful to brain nerve cells.If macrophages are not fully functional, it greatly contributes to the development of brain diseases.For example, in Alzheimer's patients, insufficient removal of harmful proteins from the blood vessels of the brain leads to a build-up of oxygen in the brain known as cerebral amyloid angiopathy."We want to use this in the future to restore or improve brain macrophage function in these types of diseases," added Prince.

Sparkling immune cells in a stroke model

The research team, led by first author Maximilian Flegov, pharmacist and PhD student at the Institute of Neuropathology at the University Hospital Freiburg, followed immune cells from the bone marrow to the brain in animal models and showed that these cells settle exclusively in the midbrain in the long term.This was done using genetically modified mice in which the immune cells were secreted and thus observed using high-resolution microscopy.Studies in stroke models have shown that disease can be influenced by metabolism."We are showing here for the first time that the immune cells of the brain vessels can be significantly changed - and the immune cells that can be changed can also be positively affected. In the next step, we want to use this knowledge to develop new treatment methods for various cerebrovascular diseases."

The study involved researchers from Freiburg and Caen (France), as well as from Bonn and Munich.

- Original title: Flagoff, M, Leward, D, Cardamom, F, et al. Specific resources and niches determine the cellular response of CNS macrophages after reimplantation.Nat Immunol (2026).DOI: https://doi.org/10.1038/s41590-026-02457-y