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US 12,748,102 B2Granted
Complex microfluidic models for ALS including NF biomarkers for ALS research and drug development
AssigneeCedars-Sinai Medical Center
InventorsSamuel Sances, Clive Svendsen
Life of this patent
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Abstract
Described herein are the effects of continuous media perfusion on SC-Chips and the observed activation of pronounced neural tissue growth and vascular recruitment into the neural tissue channel. ALS patient chip overexpression of known neurodegenerative disease biomarkers neurogranin and neurofilament family members are also described and utilized for the invention.
Claims22
A method of identifying an agent of interest, comprising:
- contacting a quantity of neurons or a quantity of ventralized spinal motor neuron progenitor cells (spNPCs) with a test agent in a top channel of a multi-channel 3-dimenional (3-D) cell culture chip;
- adding brain microvascular cells (BMECs) to a bottom channel of the multi-channel 3-D cell culture chip;
- adding culture media to the bottom channel, causing the culture media to continuously perfuse through the top or bottom channel;
- measuring biomarkers of amyotrophic lateral sclerosis (ALS) comprising one or more parameters relating to the quantity of neurons or the quantity of ventralized spNPCs, the one or more parameters being expression level of one or more genes or one or more proteins;
- and
- identifying the test agent as the agent of interest if the test agent modulates the one or more parameters by increasing or decreasing the expression level of one or more genes as compared to a reference level for each gene, or by increasing or decreasing the expression level of one or more proteins as compared to a reference level for each protein,
- wherein the quantity of neurons or the quantity of spNPCs is differentiated from induced pluripotent stem cells (iPSCs) from an ALS patient.
4 more elements
A system, comprising:
- a multi-channel 3-dimenional (3-D) cell culture chip having:
- a top channel including a quantity of neurons or a quantity of ventralized spinal motor neuron progenitor cells (spNPCs) for contacting a test agent;
- and
- a bottom channel including brain microvascular cells (BMECs) and cell culture media,
- wherein the quantity of neurons or the quantity of spNPCs is differentiated from induced pluripotent stem cells (iPSCs) from an amyotrophic lateral sclerosis (ALS) patient, and
- wherein the system is configured to perfuse the cell culture media continuously through the top or bottom channel.
3 more elements
Dependencies are inferred from the claim text.