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US 12,584,115 B2Granted
Models and methods to establish perfusable, compartmentalized, lymphoid tissue models in three-dimensional in vitro culture
AssigneeAdvanced Solutions Life Sciences, LLC
InventorsJames B. Hoying, Hannah A. Strobel, Sarah Moss
Life of this patent
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Abstract
A three-dimensional (3D) lymphoid tissue model is provided, the model including a cellularized stromal compartment and a plurality of cellularized compartments including lymphocytes disposed within the stromal compartment; and a controlled fluid perfusion system configured to perfuse the model with a perfusion fluid. Methods of fabricating a 3D lymphoid tissue model and producing antibodies with the 3D lymphoid tissue model are also provided.
Claims21
A three-dimensional (3D) lymphoid tissue model comprising:
- a cellularized stromal compartment comprising one or more stromal cell types in a stromal matrix;
- a plurality of cellularized compartments comprising
- B cells and/or peripheral blood mononuclear cells (PBMC) and a follicular matrix,
- said cellularized compartments disposed within the stromal compartment;
- and
- a controlled fluid perfusion system comprising:
- a fabricated network of microfluidic channels comprising:
- an inlet channel;
- an outlet channel;
- and
- one or more cross channels, fluidically coupling the inlet channel to the outlet channel,
- wherein:
- said microfluidic channels are defined by the stromal matrix after removal of a fugitive material;
- said network of microfluidic channels is disposed at least partially within the stromal matrix;
- an inlet port in fluid communication with the network;
- and
- an outlet port in fluid communication with the network;
- wherein said fluid perfusion system is configured to perfuse the lymphoid tissue model with a perfusion fluid.
15 more elements
A method of fabricating a 3D lymphoid tissue model, the method comprising:
- casting a network of channels on a polymerized matrix gel with a fugitive material, said network cast to form at least one perfusion inlet channel, at least one perfusion outlet channel, and one or more cross channels;
- casting pillars of lymphocytes and follicular matrix adjacent to the network of channels to generate a plurality of cellular compartments;
- incorporating stromal material with one or more stromal cell types to create a stromal matrix;
- casting the stromal matrix around the cast network of channels and the plurality of cellular compartments;
- polymerizing the stromal matrix to generate the stromal compartment;
- flushing the fugitive material from the cast network to yield a network of microfluidic channels;
- and
- subjecting the network of microfluidic channels to perfusion with a perfusion fluid.
5 more elements
Dependencies are inferred from the claim text.