Numerous neurodegenerative disorders, including Alzheimer?s Disease, glaucoma, and amyotrophic lateral sclerosis, are characterized by the degeneration of specific neuronal populations and loss of function associated with these neurons. While a number of factors may play a role in the progression of disease phenotypes within these neurons, contributions to this neurodegeneration by neighboring glia has become a topic of great interest in recent years. A variety of animal models have been used to identify and analyze these cellular contributors to neurodegeneration, however numerous differences often exist between these animal models and human systems. Thus, a critical need exists to establish effective in vitro systems with which to study cellular interactions in disease states such as Alzheimer?s Disease. Human pluripotent stem cells (hPSCs) represent a virtually unlimited source of cells for the generation of neurons affected in disease states, particularly when derived from specific patient sources. Furthermore, as these cells can give rise to all cell types of the body, the possibility also exists to derive glial cells to study non-cell autonomous contributions to neurodegeneration associated with Alzheimer?s disease, especially those contributions by astrocytes. We have previously demonstrated the ability to derive both neurons and astrocytes to create a novel in vitro model of these cellular interactions, and ongoing efforts have demonstrated the ability to effectively model features of neurodegeneration when derived from a glaucomatous source. Similarly, the opportunity exists to utilize hPSCs derived from patients with inherited forms of Alzheimer?s Disease to study the cellular interactions between cortical neurons and astrocytes. As such, an hPSC-based model of these non-cell autonomous cellular interactions between cortical neurons and astrocytes presents a powerful opportunity for the precise study of interactions between each of these cell types, including how these interactions are modulated in Alzheimer?s Disease-related neurodegeneration. Furthermore, the results of these studies will have important implications for the use of these models for the development of new therapeutic approaches to Alzheimer?s Disease.
Many neurodegenerative disorders are characterized by cell autonomous modulators of degeneration as well as non-cell autonomous contributors to the disease process. Glial cells such as astrocytes have been shown to contribute in a non-cell autonomous fashion to numerous neurodegenerative disorders, including glaucoma and Alzheimer?s Disease. The use of human pluripotent stem cells (hPSCs) can facilitate the in vitro analysis of these non-cell autonomous contributions to Alzheimer?s Disease-related neurodegeneration through the differentiation of these cells into cortical neurons and astrocytes and establishment of regulated co-cultures of these cell types.
