Bioengineered Platforms for Human Stem Cell-Based Diagnostic and Therapeutic Interventions

Abstract

Human stem cells offer an unprecedented ability to restore function lost through disease or injury by providing options for cell therapies and regenerative medicine. Two hurdles that delay greater clinical use of stem cells are production of differentiated therapeutic cells in large-scale platforms and the challenge of choosing the optimum cell type and delivery method for cell therapy that is optimized for cell-cell signaling in the therapeutic microenvironment. In my thesis work I investigated different bioengineered platforms in combination with human stem cell technology to mass produce functional hiPSC-derived beta islets in a miniature bioreactor and study cytokine release from multipotent and differentiated hiPSC-derived neural stem cells as neural rosettes and their dissociated cells or differentiating inhibitory and excitatory neurons alone and in mixed cultures applying a neural cell-cell interaction microchip (NCCIM) with features developed specifically for these studies. My work has further expanded the application of hiPSC-derived neurons in an in vitro model of traumatic brain injury. In this study a hybrid culture of hiPSC-derived excitatory pyramidal neurons, inhibitory GABAergic interneurons and immortalized human microglia are being evaluated for secreted cytokines under healthy and stretch injured induced conditions. One of the challenges of TBI is the inability to yet effectively and with minimal invasiveness track changes following injury that may indicate healing or deterioration and an in vitro model is one important contribution to identifying biomarkers.