Cedars-sinai Medical Center

Alexander Laperle

Clive N Svendsen

Samuel Sances

Nur Yucer

Described herein is a microphysiological system for models of disease. Specifically, induced pluripotent stem cells (iPSCs) and iPSC-derived cells, including those obtained from disease patients, are seeded onto microfluidic 'chip' devices to study cellular development and disease pathogenesis. Herein, neurodegenerative disease modeling, including Parkinson's Disease (PD) is shown to reproduce key PD pathology in a vascularized human model that contains neurons relating to PD pathology. Such compositions and methods are used for research for PD biomarkers, patient screening for PD risk assessment, and therapeutic discovery and testing. A panel of biomarkers are generated through analysis of living PD-chips by neural activity, whole transcriptomic, proteomic, and metabolomic analysis, and functional enzyme tests of media and tissue. Introducing therapeutics through a vasculature channel, coupled with blood brain barrier penetration studies can be assessed for efficacy in the human neural cells present in the PD-Chip.

Human pluripotent stem cell derived neurodegenerative disease models on a microfluidic chip

Described herein is functionalized glass allowing for robust attachment of extracellular matrix proteins (ECM) withstanding extended culturing periods. By first treating glass with a sulfur silane reagent, the treated glass can be activated via an amine-sulfur linker, after which ECM proteins are attached to the linker. The Inventors observed that this glass treatment combination (sulfur silane-linker-ECM) resisted degradation when compared to conventional surface coatings, such as poly-L-orthinine coated glass.

L-glass: a novel functionalization method for covalently attaching ECM protein to optical glass

Induced Pluripotent Stem Cell (Ipsc) technology enables the generation and study of living brain tissue relevant to Parkinson's disease (PD) ex vivo. Utilizing cell lines from PD patients presents a powerful discovery system that links cellular phenotypes observed in vitro with real clinical data. Differentiating patient-derived iPSCs towards a dopaminergic (DA) neural fate revealed that these cells exhibit molecular and functional properties of DA neurons in vitro that are observed to significantly degenerate in the substantia nigra of PD patients. Clinical symptoms that drive the generation of other relevant cell types may also yield novel PD-specific phenotypes in vitro that have the potential to lead to new therapeutic avenues for patients with PD. Due to their early onset and non-familial origin, differentiated nervous tissue from these patients offer a key opportunity to discover neuron subtype-specific pathological mechanisms and importantly interrogate the contribution of their genetic background in susceptibility to PD.

Growing community of inventors

North Hollywood, CA, United States of America

Alexander Laperle