Neurodegenerative disorders may meet their match with 3D micro-scaffold

The stem cell-derived neurons were found to grow and form connections on the micro-scaffold, exhibiting firing activity (seen in yellow) in response to an electrical current(Credit: Rutgers University)

Injecting reprogrammed stem cells into the brain to tackle neurodegenerative diseases isn't a new idea, but a new technique might significantly improve the effectiveness of the treatment. A team of sceintists, led by researchers at Rutgers University, has developed and conducted successful animal tests of a three-dimensional polymer micro-scaffold that dramatically improves cell survival rates following transplantation.

While implanting neurons into the brain has the potential to become an effective treatment option for combating conditions such as Parkinson's disease, past attempts have failed to produce positive results. The problem with the treatment is that the survival rates of implanted neurons is extremely low, severely limiting their potential impact.

The new work looked to improve the situation by providing the cells with a scaffold that supports the growth of neuronal connections, which are capable of transmitting electrical signals. The implanted neurons themselves are human induced pluripotent stem cells (iPSCs), which are generated from adult stem cells via the introduction of the protein NeuroD1.

The team experimented with various different polymer fibers of differing density and thickness. They eventually settled on a relatively thick polymer, and found that the amount of space between the fibers was an extremely important factor. If the fibers were arranged too loosely, then the resulting network is badly organized, but if its packed too tight there isn't enough room for the cells to properly integrate with the scaffold.

"The optimal pore size was one that was large enough for the cells to populate the scaffold, but small enough that the differentiating neurons sensed the presence of their neighbors and produced outgrowths resulting in cell-to-cell contact," said paper co-author Prabhas Moghe.

The finished micro-scaffold was tested in the lab, with the researchers implanting the tiny neuron-carrying scaffolds into brain slices from mice, via a hypodermic needle. The effectiveness of the scaffold was compared to that of individual dissociated cells, which were also injected into brain slices under laboratory conditions. The results were extremely positive, with the scaffolding increasing cell survival dramatically, while promoting neuronal outgrowth and electrical activity.

Spurred on by those findings, the researchers then injected the scaffold-support neurons into the brains of live mice, once again alongside individual cells in solution. Compared to the unsupported cells, the scaffold resulted in a 40-fold cell survival rate increase. Those cells also expressed proteins involved in neural synapse growth, which strongly indicates that the implanted neurons are capable of integrating with the host's brain and functioning as intended.

While the testing has been extremely positive, it'll be a long time before the treatment might become available to neurodegenerative disease patients. That said, the researchers are hopeful that the technique might improve treatment, and are currently working to tailor it specifically towards tackling Parkinson's disease, fine-tuning scaffold materials to optimize the survival of dopamine-producing neurons.

The findings of the research were published in the journal Nature Communications.

Source: NIH

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