ChASE37 helped human neural cells survive in rat brains after stroke
ChASE37 helped human neural cells survive in rat brains after stroke
A study published on September 9 tested a treatment for ischemic stroke in rats. Human neural progenitors, cells that can develop into neurons, survived for four weeks in 5 of 8 animals that received them together with the enzyme ChASE37. No graft was detected after transplantation of cells alone. Cells, the enzyme, and their combination improved grip strength, and the combination also changed one measure of gait.
Stroke leaves a lesion cavity and a glial scar in the brain. Proteoglycans accumulate in the scar. These large molecules occupy the space between cells and hinder the growth of nerve cell projections. Transplanted cells need to reach the lesion and remain in the altered tissue.
In the study published on September 9, the authors embedded human neural progenitors in a hyaluronic acid gel containing laminin, a protein that helps cells attach. They injected the gel into the lesion cavity on the seventh day after stroke. They applied a second gel to the brain surface above the lesion to slowly release ChASE37, an enzyme that breaks down proteoglycans in the scar.
The two gels served different purposes. ChASE37 also breaks down hyaluronic acid and would have destroyed the gel carrying the cells, so the enzyme was released from a methylcellulose gel.
This approach grew out of a 2020 study. Some members of the same team used computational methods to redesign bacterial chondroitinase ABC, an enzyme that breaks down proteoglycans. A variant with 37 amino acid substitutions remained active longer at body temperature and in a hydrogel. The current experiment tested whether an enzyme that could remain active in a gel would help transplanted cells survive in the injured brain.
One control group received saline after stroke; a second received both gels without cells or enzyme. The researchers compared these groups with groups receiving cells, ChASE37, or the combination. After four weeks, ChASE37 was still breaking down proteoglycans in the lesion. In the combination group, human cells survived in 5 of 8 rats, developed early neuronal features, and extended projections into host tissue. No graft was detected after transplantation of cells alone.
In a separate experiment, slices of the injured brain hemisphere released more FGF-2 after treatment with ChASE37. This growth factor is retained in the space between cells. The authors suggest that the release of such factors may have supported the cells. Grip strength improved after treatment with cells, the enzyme, or their combination. In the gait test, the maximum contact area of the left forepaw was greater in the combination group than in the group receiving gels without cells or enzyme.
To support the survival of human neural progenitors, the authors delivered them into the lesion cavity while modifying the surrounding scar environment for weeks.