The race is on to regenerate damaged tissue as a result of brain injury from the likes of stroke. But one of the many barriers to the success of stem cell biotechnology has been keeping cells alive long enough for them to get to work.
Typically, poor oxygen supply and a lack of a vascular network around injured brain tissue sees a high rate of cell death, among other issues, with injectable biometric hydrogel therapies.
Now, scientists have created a hybrid hydrogel that not only delivers the cells needed for tissue repair, but also provides the oxygen supply to give them the best chance of getting established at the site.
“After an injury such as a stroke, there is a dead area in the brain, including the blood system,” explained David Nisbet, professor and director of The Graeme Clark Institute for Biomedical Engineering at the University of Melbourne, Australia. “So, we need a temporary blood supply to support cells until the blood system repairs."
Developed over five years by the team, co-led by Nisbet and Australian National University professor Colin Jackson, the hybrid water-based gel contains a synthetic protein based on myoglobin that provides sustained oxygen release needed for the accompanying stem cells to survive and develop into their specialized cells.
Myoglobin is a natural protein in muscle tissue that stores and diffuses oxygen across cells. The team looked at its high prevalence in deep-diving mammals such as sperm whales and in horses, whose physiology and behaviors require sustained oxygen release.
“We observed that new tissue could be stimulated in a similar way to healthy brain tissue, providing the first evidence of the benefits of including oxygen delivery within a hydrogel to achieve the long-term survival and integrations of stem cell transplants,” said Parish.
In clinical trials with mice, led by University of Melbourne professor Clare Parish, the gel helped facilitate the survival of a greater number of cells, demonstrating improved brain tissue areas after four weeks, and holds a lot of potential to be replicated in human studies. Below, these two cross-sections illustrate a noticeable reduction in damaged (darker) tissue matter after the same period of time in the mice brain that received the myoglobin hybrid gel.
“We saw the hydrogel incorporating myoglobin and stem cells repaired injured brain tissue,” said Parish. “Analysis at 28 days after delivery of the hydrogel revealed significantly enhanced survival and growth of the new stem cells that are needed for healthy brain functioning, compared with a hydrogel without myoglobin.”
While the study highlights limitations of cell transplant technologies, such as the poor survival rate of cells within large grafts, cell degradation and diffusion away from the focal site, the researchers believe their breakthrough offers a lot of scope for the development of effective therapies.
The study was published in the journal Nature Communications.
Source: University of Melbourne
