Neurodegenerative diseases of the brain, such as Parkinson’s and Alzheimer’s, are a leading cause of disability in Canada, but despite the significant burden on patients, caregivers and the health-care system, we still lack a cure. An active area of research for these diseases is focused on the transplantation of exogenous cells to replace degenerated neurons in the brain.
Cell transplantation has demonstrated that it is beneficial in both replacing the neurons that are lost, and in secreting factors necessary for functional recovery. If we look at the example of a primate model of Parkinson’s, we see that the transplantation of dopamine neurons can restore dopamine levels and promote motor recovery.
Cells for transplantation can be taken from a variety of sources, but with the introduction of induced pluripotent stem cells (iPSCs), we can harvest a patient’s own cells and reprogram them into the desired type for replacement, making cell therapy an even more exciting prospect.
Notwithstanding the potential benefits, there are a number of issues to address before cell transplantation can be reliably implemented. One major issue is that current strategies, which generally deliver cells in a liquid medium, often result in extremely low cell survival following transplantation. There are several reasons for this: often the delivery process is rough on the cells and can trigger their death, or the local diseased environment of the brain cannot support the survival of cells.
To increase cell survival, researchers have been investigating the use of both artificially- and naturally-derived scaffolds as a vehicle for cell delivery. Scaffolds can be used to protect or cushion the cells against the shear forces generated as they are injected through the small space of a needle. To encourage cell survival and proliferation, often the chemical or physical properties of the scaffold can be adjusted to mimic the native environment of the brain. Lastly, scaffolds provide protection to the cells once they are injected into the brain by giving cells a substrate to adhere to, thereby increasing cell survival.
Recent research published in Nature Communications, from a group at Rutgers University in New Jersey, reports the use of an electrospun synthetic polymer to form a 3D scaffold to both culture and transplant cells into the brain. The researchers selected their polymer based on a library of candidates and formulated the scaffolds with either “thin” or “thick” fibres. When cells were grown on scaffolds they adhered to the fibres and were shown to form networks with cell-to-cell interactions. The authors determined that the thick fibres provided the optimal spatial orientation for cell communication and exhibited enhanced electrical activity compared to traditional 2D culture.
These types of scaffolds have been used in the past, but what makes this work exciting is that unlike with many other biomaterials, the cells do not need to be transferred from their standard culture conditions (a flask or plate) to the scaffold for transplantation, as the cells are grown on the same scaffold they are delivered in. This prevents the disruption of cell networks that form as the cells grow on the scaffold, keeping the network intact and the cells alive.
In addition to their in vitro work, the researchers constructed the scaffolds to be small enough (100µm) that after allowing a cell network to form, they could be injected through a fine-gauge needle without disrupting the network. They injected the cell-seeded scaffolds into intact mouse brains and, after three weeks, saw a 38-fold increase in cell survival compared to the transplantation of dissociated cells in a liquid medium.
While this strategy still needs to be tested in a rodent model of a neurodegenerative disease such as Parkinson’s, it is encouraging to see that the use of a scaffold to both grow and transplant an intact network of neuronal cells is possible. Strategies such as this may even allow the transplantation of a network of several neuron subtypes that mimics the complex organization of the brain.
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