Scientists develop method to grow brain cells lost in Huntington’s
Transplanting cells in mouse model found to 'markedly' reverse motor deficits
Researchers in China have developed a new system to grow the specific type of brain cells that are lost in Huntington’s disease, and have seen benefits in testing it in a mouse model of the neurodegenerative disorder.
Transplanting these cells into the brains of the animal model lessened the mice’s motor problems — results that Unixell Biotechnology, the cell therapy company developing the system, “deemed promising” in a press release.
“Following transplantation, the cells [successfully] integrated into host neural circuits and markedly reversed motor deficits in Huntington’s disease models,” said Yuejun Chen, PhD, the study’s corresponding author and founder of Unixell.
The results provide “a decisive proof-of-principle for Unixell’s cell-replacement therapy pipeline and for next-generation therapies against neurodegenerative disorders,” Chen added.
The findings were described in “3D cultured human medium spiny neurons functionally integrate and rescue motor deficits in Huntington’s disease mice,” a study published in The Journal of Clinical Investigation. Chen’s team collaborated closely with Xiong Lab at Fudan University in Shanghai.
Huntington’s is a genetic disorder marked by the degeneration and death of brain cells. A specific type of nerve cell in the brain, called medium spiny neurons, or MSNs, is particularly hard hit in people with Huntington’s.
New cells showed features consistent with those in the human brain
Pluripotent stem cells are specialized cells that are able to grow into many other types of cells. These stem cells play crucial roles in early development, and researchers have also devised ways to generate them in labs. But growing stem cells into any specific type of cell, like MSNs, requires giving the stem cells a very specific set of chemical cues.
Chen and colleagues in China developed a novel protocol, named 3D-default XFS, to grow human stem cells into lateral ganglionic eminence (LGE) neural progenitor cells — immature cells that are able to grow into mature MSNs.
The scientists showed that the MSNs generated through this protocol display molecular features consistent with MSNs found in the brain. In particular, the team noted that 3D-default XFS follows all regulatory requirements that would be needed to produce cells for commercial use as a therapy.
“These results demonstrate that 3D-default XFSC efficiently generates LGE neural progenitors and MSN subtypes that closely resemble their fetal counterparts,” the team wrote.
[These findings, while in a mouse model, suggest] promising potential for using these cells in future applications.
The scientists then transplanted the generated cells into the brains of a mouse model of Huntington’s. The team found that the transplanted cells were able to grow and form connections with other brain regions in much the same way that normally occurring MSNs do.
Huntington’s mice given this brain cell transplant also showed significant improvements in measures of motor function at two and five months after the procedure. Motor performance on some tests even reached that of healthy mice, while there was only a partial rescue on other tests.
“Together, these data indicate that [MSNs generated through the new protocol] integrated into host neural circuits and restored motor deficits in [Huntington’s disease] model mice in the long term,” the researchers wrote.
Added Chen: “This study establishes a chemically-defined, 3D suspension platform that … [enables] robust, scalable generation of authentic human MSN subtypes.”
Although these experiments were done in mice and more work is needed, the scientists said these findings suggest “promising potential for using these cells in future applications.”
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