Stem cell therapy reverses stroke damage in mice

Recovery was observed in mice receiving a stem cell transplant post-stroke, according to new research.

Researchers have successfully transplanted human induced pluripotent stem cell-derived neural progenitor cells (NPCs) – cells at the early stages of becoming neurons – into mice that had a stroke ten days prior. The study published in Nature Communications, determined that therapy for stroke could be administered days after the first symptoms appear and still aid in recovery.

'Our findings show that neural stem cells not only form new neurons, but also induce other regeneration processes,' said co-corresponding author Dr Christian Tackenberg, scientific head of division in the neurodegeneration group at the University of Zurich Institute for Regenerative Medicine in Switzerland. 'We found that the stem cells survived for the full analysis period of five weeks and that most of them transformed into neurons, which actually even communicated with the already existing brain cells.'

A stroke is caused by a ruptured or blocked blood vessel that disrupts blood flow to the brain. One in four adults will have a stroke in their lifetime, and with no effective treatment, half of those will exhibit long-term disability such as paralysis or speech impairment.

By using genetically-modified mice to prevent rejection, the researchers measured improvement in the mice post-transplant via use of a free walking runway and a horizontal ladder.

The mice that received the human NPC transplant showed greater improvement in their walking and climbing movements, as well as their fine-motor recovery, compared to the groups who had an induced stroke but placebo surgery with no transplant.

Furthermore, the brains of mice treated with the NPCs also showed that they had differentiated into mature neurons, helping regenerate damaged tissue through the formation of new blood vessels, reducing inflammation, repairing the blood-brain barrier, and aiding the formation of new neurons.

To understand the underlying mechanisms, the scientists studied the types of cells that die during a stroke. They found that neurons that secrete the neurotransmitter gamma-aminobutyric acid (GABA) were reduced by just over 50 percent.

By using single-nucleus RNA sequencing, the researchers determined that the majority of the transplanted NPCs differentiated into GABA-secreting neurons – suggesting that these neurons are essential for aiding stroke recovery. From analysing the interactions between the transplanted cells and other mouse brain cells, the researchers uncovered activity in different signalling pathways associated with regenerating neurons, guiding how neurons form connections with each other.

'If we can help people by transplanting stem cells into a human stroke patient, we want the cells to be there for the rest of their life,' said co-corresponding author Dr Ruslan Rust, assistant professor of research physiology and neuroscience at the Keck School of Medicine of the University of Southern California. 'So our aim would be to look across the whole lifetime of a mouse and see what happens with the cells, and also see whether this recovery is sustained or even improves.'