A new hydrogel matrix appears to ease the delivery of therapeutic stem cells into the brain, a necessary step in potentially using these cells to treat Parkinson’s disease.
In animal models, this hydrogel was found to provide a safe scaffold for stem cells to differentiate into dopamine-producing nerve cells — those gradually lost in Parkinson’s — improving the animals’ motor function.
In Parkinson’s, neurons responsible for producing dopamine, called dopaminergic neurons, in the brain begin to malfunction or die, leading to disease symptoms. Stem cells — cells that can divide and differentiate into almost any type of cell — have attracted interest as a Parkinson’s therapy as they have the potential to replace the defective or lost neurons.
During delivery to the brain, however, stem cell-derived dopaminergic progenitors are exposed to stresses that can be deadly.
“The number of [dopaminergic] neurons that survive in a graft is recognized as the most decisive factor in governing whether a transplant is successful in ameliorating symptoms, yet cell survival remains a major challenge for the field,” the researchers wrote.
Scientists in Australia report designing and testing a well-defined structure, called a hydrogel matrix made from amino acids (the building blocks of proteins). It is also rich in a growth-stimulating protein called GDNF that helps cells survive, grow, and differentiate.
The gel was loaded with human stem cell-derived neuron progenitors, and injected into the brains of mice and rats.
“When we shake or apply energy to the hydrogel, the substance turns into a liquid which allows us to inject it into the brain through a very small capillary using a needle,” David Nisbet, PhD, a professor at the Australian National University John Curtin School of Medical Research and a study lead author, said in a press release.
“Once inside the brain, the gel returns to its solid form and provides support for the stem cells to replace lost dopamine neurons,” Nisbet added.
Compared with stem cells alone, a greater percentage (51% increase) of stem cells delivered along with the hydrogel turned into a type of dopamine-producing neuron that is critical for motor function.
Importantly, the release of GDNF from the hydrogel increased the number of dopamine-producing neurons by 2.7 fold, resulting in improvements in recipients’ motor function at six months post-transplant.
“In animals receiving these cell grafts supported by the GDNF-functionalized hydrogel, both induced and spontaneous motor deficits were ameliorated,” the researchers wrote.
While several available Parkinson’s treatments focus on increasing dopamine levels in the brains of patients, their side effects are known to worsen with time. Alternative treatment approaches are needed.
“The stem cell transplant delivered in this hydrogel on the other hand avoids many of these side effects and could provide a one-off intervention that can sustain dopamine levels for decades to come,” said Clare Parish, PhD, head of the Stem Cell and Neural Development Laboratory at The Florey Institute.
The gel is thought to be cost-effective and easy to make in large quantities, but more testing and refinement is needed before it might be considered for use in patients.
“These findings highlight the potential therapeutic benefit of customized hydrogels to support [human-derived] neural transplants in brain repair,” the researchers wrote.
“Further studies targeting additional/alternative proteins for neuroprotection, plasticity, and vascularization, are necessary to ensure maximal functional benefits can be obtained from grafted progenitors,” they added, both as a Parkinson’s cell therapy and a therapy for other conditions, like stroke, “where cell transplantation presents a therapeutically viable option.”