First steps towards cell therapy of brain diseases - University of Freiburg

The first step towards cell therapy for brain diseases

Freiburg researchers have found a way to selectively replace defective immune cells in the brain in animal models.This is an important first step in the treatment of Alzheimer's cells and other brain diseases.The results were published in the journal Nature Immunology.

An artist's view of the border areas of the brain from the dura mater to the brain, showing groups of resident macrophages (blue) and infiltrating monocyte-derived macrophages (yellow).Photo: Freiburg University Hospital / Maximilian Fliegauf

The brain and its connections are controlled by specialized immune cells.Scientists from the Faculty of Medicine at the University of Freiburg have now studied the phagocytes in the meninges and blood vessels of the brain, which regulate the removal of waste products from the brain and control the inflammatory process.As shown by scientists from the Institute of Neuropathology of the University Hospital of Freiburg with an international research team, the short administration of the drug causes controlled cell death in these cells.As a result, they are replaced by new cells, which affects their function.In the future, this method may be the basis of a new treatment against the harmful vascular deposits in Alzheimer's disease.The research, published in the journal Nature Immunology, was conducted on a modified mouse line.The data obtained is an important element to enable the use of cell therapy in brain diseases.

"With our method, we can selectively replace phagocytes, also called macrophages, in the blood vessels of the brain. Macrophages in the brain, which are located right next to sensitive nerve cells, remain unchanged," says the head of the study, Prof. Dr. Marco Prinz, Medical Director of the Institute of Neuropathology at the University Hospital Freiburg and member of the CIB Biological CIB Signaling Center of Excellence. Studied at the University of Freiburg."All the cells that we examined are part of the blood-brain barrier, which makes it very difficult to access therapeutic preparations. The fact that we can now specifically replace the macrophages for the first time is a great advance," adds Dr. Lukas Amann, head of the group at the Institute of Neuropathology at the University Hospital Freiburg and the last author of the study.

The brain can be divided into two regions: the border region and the functional organization.In both cases, macrophages are the primary immune cells.Macrophages at the brain interface are located directly on the blood-brain barrier formed by blood vessels in the brain.There, it controls which substances penetrate the brain and protects it from harmful substances, deposits, and pathogens.At the same time, waste products from the brain are also removed by blood vessels, and macrophages play an important regulatory role.

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

It is important for Alzheimer's, etc.

"Removing waste products from the brain is very important because they are very damaging to the brain's nerve cells. If macrophages are not fully functional, this contributes significantly to the development of brain diseases. For example, in Alzheimer's patients, inadequate removal of harmful proteins from the brain's blood vessels leads to so-calpathoyl protein accumulation. Oxygen supply to the brain is impaired, which can lead to memory loss and hemorrhage.

Bright immune cells in stroke sample

A research team led by first author Maximilian Pligauf, a pharmacist and doctoral student at the Institute of Neuropathology at the University Hospital Freiburg, followed the cells of the immune system from the bone marrow to the brain in an animal model and showed that these cells reside at the brain interface for an especially long time.This was done using genetically engineered mice in which the immune cells were made luminescent so they could be viewed using high-resolution microscopy.Studies have shown that diseases can be influenced by metabolism."We show here for the first time that the immune cells of the brain vessels can be specifically replaced - and that the immune cells that can be replaced can also be positively influenced. In the next step, we want to use this knowledge to develop new therapeutic approaches for various vascular diseases in the brain."

Scientists from Freiburg and Caen (France), as well as Bonn and Munich participated in the research.

- Original study title: Fliegauf, M., Levard, D., Cardamone, F. et al.Distinct origins and niches determine the cellular response of CNS macrophages after regeneration.Nat Immunol (2026). DOI: https://doi.org/10.1038/s41590-026-02457-y