Researchers from the Indian Institute of Technology, Bombay (IIT B) have taken the first successful step at regenerating neurons in a Parkinson mouse model by using mesenchymal stem cells (MSCs) encapsulated in an amyloid hydrogel. The hydrogels which provide scaffolding for stem cells to develop into neurons when implanted in the brain are developed from a special class of proteins called amyloids. The results were published in the journal NPG Asia Materials.
The hydrogel enabled the delivery and engraftment of mesenchymal stem cells in two regions of the mice brain - substantia nigra and striatum - where the cells were injected. “We do not have direct proof that mesenchymal stem cells have become neurons. But the stem cells transplanted at the substantia nigra site were differentiating into neuron-like cells,” says Subhadeep Das from IITB-Monash Research Academy, IIT Bombay and the first author of the paper.
“We wanted to first know if the cells were surviving and were contained at the site. So the time point was short, and we sacrificed the animals at the end of the seventh day after transplantation,” he says. “Further studies for prolonged periods will tell if the mesenchymal stem cells become matured neurons.”
In the case of Parkinson’s, neurons based in the substantia nigra region of the brain release dopamine at the striatum. Since the connection between the two regions is lost in the case of Parkinson’s, the researchers implanted the stem cells at both the sites.
But before transplanting the stem cells encapsulated in the hydrogel into the brain of the mice, the researchers tested the hydrogel in the lab for toxicity. Both neural precursor cell lines and mesenchymal stem cells were cultured in the amyloid hydrogel. And 2D and 3D culture tests for toxicity were carried out for both short (24 hours) and long (120 hours) term and the results compared with a collagen hydrogel, which served as control. “The compatibility of amyloid hydrogel was similar to collagen,” says Das.
Besides being a good scaffold that facilitates the differentiation of stem cells into neurons and not being toxic, the hydrogel should also not trigger the immune system from mounting a violent reaction against it when implanted into the brain. So the researchers injected the hydrogel into rat brain to test for any possible inflammatory response or immune rejection of the amyloid hydrogel. While two types of inflammatory cells - microglia and atrocytes - accumulated near the hydrogel, their levels subsided by 21 days.
In a next step, they implanted the hydrogel containing the mesenchymal stem cells in the brain of the Parkinson mouse model. “The hydrogel was able to improve the viability of the transplanted cells and were able to contain them at the site where they were implanted,” says Das. The control cells that were not contained in hydrogel were three times less viable than the cells contained in the hydrogel.
“Amyloids are among the most robust protein/peptide-based materials ever evolved in nature. We just utilised these superior materials property of amyloids for targeting stem cell delivery in the brain and their differentiation to neurons. On the one hand, amyloid-based hydrogels are capable of protecting delicate stem cells within the hydrogels matrix, while on the other hand, they are able to guide the differentiation of stem cells towards neurons,” Samir K. Maji from the Department of Biosciences and Bioengineering, IIT Bombay and the corresponding author of the paper says in a release.
There are three major challenges when stem cells are transplanted or injected into the brain - the cells should survive, should not migrate to different places where they are not required, and should become functional neurons and integrate with the existing neural circuit. “Our material has solved the first two challenges. We are now working on the third one,” says Das confidently.
