Abstract
Human induced pluripotent stem cells (iPSCs) can be used to model complex diseases in human-relevant in vitro platforms. iPSC lines can be reprogrammed from patient blood cells and fibroblasts and differentiated into endpoint cells covering the central and peripheral nervous systems, the cardiovascular system and skeletal muscle.
Human iPSC-derived cells can be produced from patients with complex diseases including Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s Disease and Parkinson’s Disease, and incorporated into in vitro models for research and drug discovery1,2. Combining these cells with micro-physiological systems (MPS) can better mimic the relationship between human cell types in vivo, providing more complex in vitro models of human disease.
Here we demonstrate the use of multiple MPS platforms with human iPSC-derived neuronal cell types to build models of human neurodegenerative disease and pain. The compatibility of iPSC-derived neuronal cell types and MPS platforms is key to the success of establishing complex biological interactions; we outline here a variety of critical parameters identified for creating a successful culture within the MPS platforms. Targeted and established biocompatibility enables methodologies to measure cell-to-cell interactions via multimodal endpoints, including immunocytochemistry, cytokine release, neurite outgrowth and multi-electrode array (MEA).
We also provide examples of complex human iPSC-based models. These include 2D and 3D neuromuscular junction (NMJ) models using iPSC-derived skeletal muscle and motor neurons (to study specific disease-relevant targets in ALS) and simple monoculture systems using iPSC-derived motor neurons or sensory neurons for axotomy, pain and itch models for drug discovery.
