Cedars-Sinai Medical Center

Emulate, Inc.

Wisconsin Alumni Research Foundation

Gad Vatine

Clive N Svendsen

Daniel Levner

Christopher David Hinojosa

Geraldine A Hamilton

Norman Wen

Jacob Fraser

Dhruv Sareen

Samuel Sances

S Jordan Kerns

Carolina Lucchesi

Sean Paul Palecek

Eric V Shusta

Chris Hinojosa

Carol Lucchesi

Brandon Shelley

SJordan Kerns

Scott G Canfield

Samuel Sanees

Sam Sances

Geraldine Hamilton

Alexis J Kerl

Clive Svendsen

The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.

Microfluidic model of the blood brain barrier

Development of spinal cord on a microfluidic chip

A method of creating an isogenic multicellular blood-brain barrier model from iPSCs is disclosed.

Isogenic blood-brain barrier model

Brain microvascular endothelial cells (BMECS) can be generated from pluripotent stem cells, and possess membrane barrier functions along with capability for maturation into other developing tissues. This cell type has not been successfully frozen with loss of significant viability and/or BMEC functional properties. For example, BMECs can be used to model barrier function in blood brain barrier, by calculating the trans-endothelial resistance (TEER). However, thawed primary BMECs lose TEER resistance. By optimizing cell preparation, freezing media selection, and the controlled freezing, the Inventors have achieved complete recovery of frozen cells, achieving proper tight junction protein expression and physiologically relevant TEER. The freezing methods and compositions described herein, thereby allow for BMECs to be manufactured, frozen and distributed at scale.

Methods and compositions for cryopreservation of endothelial cells

Growing community of inventors

Los Angeles, CA, United States of America

Gad Vatine