Washington | Scientists, including one of Indian-origin, have created a 3D micro-scaffold that promotes the reprogramming of stem cells into neurons and supports the growth of neuronal connections capable of transmitting electrical signals.
The platform could make transplantation of neurons a viable treatment for a broad range of human neurodegenerative disorders, researchers said. The injection of these networks of functioning human neural cells – compared to injecting individual cells – dramatically improved their survival following transplantation into mouse brains.
Previously, transplantation of neurons to treat neurodegenerative disorders, such as Parkinson’s disease, had very limited success due to poor survival of neurons that were injected as a solution of individual cells. The researchers, including those from Rutgers University and Stanford University in US, experimented in creating scaffolds made of different types of polymer fibres, and of varying thickness and density. They ultimately created a web of relatively thick fibre’s using a polymer that stem cells successfully adhered to.
Researchers used human induced pluripotent stem cells (iPSCs), which can be readily generated from adult cell types such as skin cells. The iPSCs were induced to differentiate into neural cells by introducing the protein NeuroD1 into the cells. The space between the polymer fibres turned out to be critical. 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 neighbours and produced outgrowths resulting in cell-to-cell contact, said Prabhas Moghe, professor at Rutgers University. This contact enhances cell survival and development into functional neurons able to transmit an electrical signal across the developing neural network, said Moghe.
To test the viability of neuron-seeded scaffolds when transplanted, the researchers created micro-scaffolds that were small enough for injection into mouse brain tissue using a standard hypodermic needle. They injected scaffolds carrying the human neurons into brain slices from mice and compared them to human neurons injected as individual, dissociated cells. The neurons on the scaffolds had dramatically increased cell-survival compared with the individual cell suspensions.
The scaffolds also promoted improved neuronal outgrowth and electrical activity. Neurons injected individually resulted in very few cells surviving the transplant procedure. Human neurons on scaffolds compared to neurons in solution were then tested when injected into the brains of live mice. Similar to the results in the brain slices, the survival rate of neurons on the scaffold network was increased nearly 40-fold compared to injected isolated cells.