Development and Plasticity of Stem/Progenitor Cells Investigated using Integrated Chips-Based and Microfluidic Devices.

Research in the Sakaguchi lab is focused on developing experimental strategies for brain and retinal rescue and repair. As a potential therapy for the treatment of neurodegenerative diseases and injury, stem cells have been proposed as unique sources of transplantable cells to provide neuroprotection and to replace degenerating neurons and glial cells.

Significant efforts for studying neurodegenerative diseases and brain injury often implement animal-based models. However, these in vivo approaches have significant inherent limitations, including ethical approval, high costs, and low throughput, and are labor-intensive and time-consuming processes, often with considerable experimental variations. In contrast, in vitro models can avoid these issues, allowing high-throughput drug screening and disease modeling, and are more cost-effective, and are ideal alternatives. 

To improve our understanding of how the brain and retina function in health and disease, we are collaborating with engineers to develop integrated chip-based technologies to study the effects of bioactive molecules (neurotransmitters, neurotrophic growth factors, and cytokines) and electrical and magnetic stimulation on the development and differentiation of brain and retinal-derived stem/progenitor cells. In addition, microfluidic devices are designed and fabricated, incorporating tunable diffusion barriers and real-time chemical sensors. Under the appropriate conditions, the neural progenitor cells used in these studies can self-assemble and maintain their proliferative capacity to generate three-dimensional (3D) cellular aggregates, referred to as neurospheres or retinospheres, respectively, when cultured in the absence of exogenous extracellular matrix proteins.