3D spheroid-based brain model to study the effects of electrical stimulation on recovery following a stroke
Jennifer H. Shin
Abstract : Stroke, caused by cerebral blood flow abnormalities, can endanger the life of a patient and leaves a severe aftereffect. Based on recent findings on the efficacy of noninvasive electrical stimulation for the promotion of neuroplasticity, several attempts have been made to treat stroke with electrical means. Despite their importance and attempts, the exact mechanism of how the electrical field (EF) stimulation regulates neural plasticity remains elusive. One of the significant limitations is the lack of an appropriate in vitro model. In vitro models have significant advantages in identifying reaction mechanisms by limiting the number and type of cells as well as controlling various environmental conditions to reduce variables. Therefore, our research team developed an in vitro brain model that can simulate the three-dimensional microenvironment of the brain by aggregating brain cells into 3D spheroids on low affinity surfaces, and followed by oxygen-glucose deprivation and reperfusion (5% CO2, 94% N2, 1% O2, 3 hours) to establish a stroke model. Based on gene and morphological analyses, we confirmed that the 3D spheroid-based stroke model adequately simulates the traits of the in vivo animal stroke models. The EF stimulation platform was then constructed with a non-sticking agar substrate to maintain the morphological and, thus, the functional integrity of the spheroids during EF stimulation. Upon EF stimulation for as short as 15 mins at 2V/cm, it was clear that two in vitro models, normal and stroke, exhibited different sensitivity to the EF, and responded differently. In the normal brain model, all genes involved in neuroplasticity (ARC, CREB, NR2A, MAP2) were enhanced by the EF stimulation, whereas the stroke model showed much less sensitivity to the EF. Now, our next goal would be to identify the key regulations responsible for the suppressed functionality in the stroke model and to seek the right conditions of the EF stimulation at which the brain cells of the stroke model would respond positively for better recovery.
Bio : Jennifer H. Shin is a professor in the Mechanical Engineering (ME) Department at KAIST. She received B.S., M.S., and Ph.D. in ME at MIT in 1998, 2000, and 2004, respectively. Dr. Shin’s research interests center around the emerging interdisciplinary mechanobiology. Her research focuses on finding links between cellular biomechanics and physiological changes associated with diseases in light of diagnostics and therapeutics. She has been an active board member for 7 academic societies across the fields of core mechanical engineering and biomedical engineering. She served an active organizing committee for many international conferences including Biofabrication, microTAS, IBEC, ISPIV, and IEEE-EMBC, and is an elected member of the Executive Council of the International Society of Biomechanics (ISB). In particular, Dr. Shin has displayed genuine passion and enthusiasm for teaching students and was recognized with several teaching excellence awards both at the departmental and institutional levels. She received GASAN Academic Award from Korean Society of Mechanical Engineers in 2018 in recognition of her contribution in Fluid Engineering Fields.
