Stem Cell Transplant Helps Brain Recover From Stroke in Groundbreaking Study

Scientists have shown that transplanting lab-grown neural stem cells can help the brain regenerate after a stroke. In tests on mice, these cells formed new neurons, reduced inflammation, and improved the animals' movement. The cells also communicated with those in the brain itself, helping rebuild nerve connections. The research paves the way for therapies that can restore the human brain after a stroke.

Ischemic stroke occurs when blood flow to a part of the brain is blocked, depriving brain cells of oxygen and nutrients. It is a leading cause of death and disability worldwide, affecting about one in four people over the course of their lives.

Even with available treatments, such as thrombolysis (the use of medications that dissolve the clot) and mechanical thrombectomy (the physical removal of the clot), many patients remain with permanent limitations, as these therapies can only be administered in the first hours after a stroke and carry considerable risks.

In recent years, scientists have been investigating the use of stem cells as a new way to treat stroke. These cells are unique because they can transform into different types of cells in the body, aiding in tissue regeneration.

In animal studies, stem cell transplantation has shown significant benefits: reducing inflammation, stimulating the formation of new blood vessels and neurons, rebuilding nerve connections, and even repairing the blood-brain barrier (the blood-brain barrier). However, clinical trials in humans have not yet been able to consistently reproduce these promising results.

With the advancement of cell biology technologies, a powerful new tool has emerged: induced pluripotent stem cells (called iPSCs). These are obtained from the patient's own cells, such as skin cells, which are "reprogrammed" in the laboratory to return to a state similar to that of an embryonic stem cell.

These iPSCs can then be guided to transform into neural progenitor cells (NPCs), precursor cells that can give rise to neurons and other cells of the nervous system. This technology is promising because it avoids ethical dilemmas, can be personalized for each patient, and reduces the risk of immune rejection.

The study in question investigated the use of these iPSC-derived NPCs in mice with brain damage caused by stroke. The researchers transplanted the NPCs directly into the injured area of ​​the brain, near the cerebral infarction site, and monitored the animals for five weeks.

Human neural stem cells in culture. Cell nuclei are stained blue, the neural stem cell-specific filamentous protein Nestin is shown in green, and the neural stem cell transcription factor Sox1 is shown in red. Credit: University of Zurich

They observed that mice treated with the cells showed better recovery compared to those given only a placebo. The beneficial effects included reduced inflammation, increased growth of new blood vessels (angiogenesis), and increased formation of new neurons and axons (neurogenesis and axonogenesis).

In addition to microscopic analyses, the researchers also assessed the animals' behavior and motor recovery using modern machine learning (artificial intelligence) technologies, which allowed them to accurately measure the mice's movement, coordination, and gait. The results showed significant improvements in motor function and walking ability in the animals treated with NPCs.

This image shows the brain of a mouse that suffered a stroke and received a transplant of human neural progenitor cells, cells capable of developing into neurons and aiding brain regeneration. The dashed circle marks the area affected by the stroke. The dark brown structures represent the nerve projections (neurites) of the transplanted human cells, which grew within the mouse's brain. These new nerve extensions were not restricted to the transplant site: they extended to nearby regions of the cerebral cortex (CX) and also traversed the corpus callosum (CC), the fiber bridge that connects the two hemispheres of the brain, reaching the other side of the brain. In section G, the drawing shows the position of the brain slices (viewed from the side) that were analyzed in the following images. Images H to J show brain sections stained specifically for a human protein called NCAM, which identifies the grafted human cells. The black bars indicate a scale of 100 micrometers, meaning the image shows very small structures, visible only under a microscope. Finally, panel K shows, in map form, the percentage of animals in which the transplanted cells were able to send nerve projections to different brain regions, indicating the successful integration of human cells into the mouse brain.

By examining the transplanted cells, the scientists found that most of them had transformed into GABAergic neurons, which are cells responsible for regulating the brain's electrical activity, acting as "brakes" for the nervous system.

Detailed molecular analyses using single-cell RNA sequencing, a technique that allows studying the active genes in each cell individually, showed that there was intense communication between the transplanted cells and the host brain cells. This interaction appears to occur through signaling pathways known as Neurexin, Neuregulin, NCAM, and SLIT, which are involved in the formation and repair of neural connections.

In summary, the study demonstrated that iPSC-derived neural progenitor cells can survive, integrate, and aid in brain regeneration after stroke, improving both brain structure and function. This discovery offers new insights into how cell transplants can work to restore damaged circuits and reinforces the therapeutic potential of this approach for stroke patients in the future.

READ MORE:

Neural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk 

Rebecca Z. Weber, Beatriz Achón Buil, Nora H. Rentsch, Patrick Perron, Stefanie Halliday, Allison Bosworth, Mingzi Zhang, Kassandra Kisler, Chantal Bodenmann, Kathrin J. Zürcher, Daniela Uhr, Debora Meier, Siri L. Peter, Melanie Generali, Shuo Lin, Markus A. Rüegg, Roger M. Nitsch, Christian Tackenberg, and Ruslan Rust

Nature Communications. 16, Article number: 8224 (2025) 

DOI: 10.1038/s41467-025-63725-3

Abstract: 

Stroke remains a leading cause of disability due to the brain’s limited ability to regenerate damaged neural circuits. Here, we show that local transplantation of iPSC-derived neural progenitor cells (NPCs) improves brain repair and long-term functional recovery in stroke-injured mice. NPCs survive for over five weeks, differentiate primarily into mature neurons, and contribute to regeneration-associated tissue responses including angiogenesis, blood–brain barrier repair, reduced inflammation, and neurogenesis. NPC-treated mice show improved gait and fine-motor recovery, as quantified by deep learning-based analysis. Single-nucleus RNA sequencing reveals that grafts predominantly adopt GABAergic and glutamatergic phenotypes, with GABAergic cells engaging in graft-host crosstalk via neurexin, neuregulin, neural cell adhesion molecule, and SLIT signaling pathways. Our findings provide mechanistic insight into how neural xenografts interact with host stroke tissue to drive structural and functional repair. These results support the therapeutic potential of NPC transplantation for promoting long-term recovery after stroke.