UC Irvine

Induced pluripotent stem cells (iPSC) have opened a new direction on study of Alzheimer’s Disease due to their pluripotency. Differentiation of iPSC to neurons has been cultured in 2D successfully with solid proof including morphological, electrophysiological and immunological, but the yield is low and unpredictable. However, 3D culture of neurons might be better approach human physiology. As a result, differentiation of iPSCs to neurons in a 3D environment has become a new research topic. We obtained 3 different iPSC cell lines from fibroblasts of, non-demented, mild cognitive impaired and demented human subjects. We differentiated these iPSCs first to neural stem cells (NSC) by neural induction, then into neurons on multi-electrode arrays to measure network electrical activity. We also cultured rat hippocampal neurons in both 2D and 3D environment of Matrigel on the MEAs to compare their average spike rate and average inter spike interval. The 3D cultures of rat neurons indicate a need for further optimization of the 3D matrix. The low yields of neuroprogenitors and neurons from human iPSC suggest a need for better control of the initial generation of the pluripotency of the iPSC.