Mechanisms of Alzheimer's disease have been mimicked in a novel, stem cell-based model system that reproduces features of human brain tissue. This experimental tool can be used to help to find new therapeutic approaches, according an international team of researchers. Their results, published in Developmental Cell today, indicate that modulating the immune system can trigger neuronal repair processes and thus possibly help the brain to better cope with Alzheimer's.
By using the new disease model, the researchers discovered an approach to instruct stem cells to produce neurons. This kick-started repair processes. "Neural stem cells are the progenitors of neurons. They occur naturally in the brain and as such they constitute a reservoir for new neurons. However, in Alzheimer's neural stem cells lose this ability and therefore cannot replace neurons lost due to the disease," explains Caghan Kizil, head of the current study and research group leader at the German Center for Neurodegenerative Diseases (DZNE). "Our results suggest that modulating the immune system can unlock the potential of neural stem cells to build new neurons. These new cells foster regeneration and could possibly help the brain to better cope with the disease."
The new disease model is based on human stem cells that are embedded in a polymer hydrogels. This soft and transparent biomaterial consists of the glycosaminoglycan heparin, the synthetic polymer poly(ethylene glycol), and various functional peptide units. The cell cultures are then grown in small culture wells of less than one milliliter volume. "The tunable polymer system allowed to combine effective molecular and physical signals that direct the cells to generate three-dimensional networks reminiscent of the neuronal webs of the human brain," emphasizes Carsten Werner, director of the biomaterials program at the Leibniz Institute of Polymer Research Dresden (IPF).
"Other disease models based on human stem cells already exist. However, they are not suitable to address questions of our research on neuronal regeneration," Kizil explains. "We are confident, that our system is unprecedented in several aspects such as the ability of stem cells to behave in a similar way as they do in the brain."
Thus, Kizil sees various applications: "Because of these properties, our model could be of use not only to study disease processes. I also see use in the pharmaceutical industry. Here, it could be applied in the early phase of drug development for the testing of chemical compounds."