Cedars-sinai Medical Center

Emulate, Inc.

Other

Dhruv Sareen

Clive N Svendsen

Daniel Levner

Christopher David Hinojosa

Geraldine A Hamilton

Norman Wen

Jacob Fraser

S Jordan Kerns

Robert N Barrett

Carol Lucchesi

Gad Vatine

Michael Workman

Loren A Ornelas

Uthra Rajamani

Carolina Lucchesi

Magdalena Kasendra

Jefferson Puerta

Samuel Sances

Stephen R Targan

Chris Hinojosa

Stephan R Targan

Catherine Karalis

Xiaojiang Cui

Ville Kujala

Samuel Sanees

SJordan Kerns

Armando E Giuliano

Ying Qu

Andrew R Gross

Berhan Mandefro

Anjoscha Kaus

Sam Sances

Hyoung Shin Park

Jordan Kerns

Magdelena Kasendra

Alexis J Kerl

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

Organs-on-chips are microfluidic devices for culturing living cells in micrometer sized chambers in order to model physiological functions of tissues and organs. Engineered patterning and continuous fluid flow in these devices has allowed culturing of intestinal cells bearing physiologically relevant features and sustained exposure to bacteria while maintaining cellular viability, thereby allowing study of inflammatory bowl diseases. However, existing intestinal cells do not possess all physiologically relevant subtypes, do not possess the repertoire of genetic variations, or allow for study of other important cellular actors such as immune cells. Use of iPSC-derived epithelium, including IBD patient-specific cells, allows for superior disease modeling by capturing the multi-faceted nature of the disease.

Systems and methods for growth of intestinal cells in microfluidic devices

Bioprinting is the layer-by-layer construction of synthetic tissues or scaffolds. Described herein is a motorized extruder which can precisely extrude and retract extrudate such as bioinks in a compact and rapidly-loadable form-factor. This includes a compact bioprinter using a stepper motor coupled with a threaded shaft to directly move the plunger of an extruder. This pneumatic-mechanical system obviates the needs for pneumatic tubing, rods, or other complex elements of existing designs. The direct drive design further allows for a lighter, smaller gantry that is capable of more precise fabrication of bioprinted constructions. This includes delicate vasculature systems that are beyond limits of existing bioprinting technologies.

Compact mechanical syringe extruder for 3D bioprinting of cell laden gels

Development of spinal cord on a microfluidic chip

Type 2 diabetes (T2D) is a clinical syndrome caused by insufficient insulin secretion for insulin requirements. described herein are compositions and methods for microphysiological MPS models of disease (MODs) for diabetes. These platforms allow one to compare the effect of chronic β-cell stimulation in the presence and absence of patient specific immune cells in IPSC-derived islets from each group. Additionally, one can reproduce the T2D β-cell phenotype, using islets-on-chips will also be exposed to gluco-lipotoxicity. Likewise, skeletal muscle-on-chips are exposed to patient specific activated immune cells, variable motor neuron innervation and lipids characteristic of T2D.

Methods of use of islet cells

Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.

Method for reprogramming blood to induced pluripotent stem cells

Human induced pluripotent stem cells (iPSCs) can give rise to multiple cell types and hold great promise in regenerative medicine and disease modeling applications. The Inventors herein developed a reliable two-step protocol to generate human mammary-like organoids from iPSCs. Non-neural ectoderm cell-containing spheres, referred to as mEBs, were first differentiated and enriched from iPSCs using MammoCult medium. Gene expression profile analysis suggested that mammary gland function-associated signaling pathways were hallmarks of 10-d differentiated mEBs. The Inventors generated mammary-like organoids from 10-d mEBs using 3D floating mixed gel culture and a three-stage differentiation procedure. These organoids expressed common breast tissue, luminal, and basal markers, including estrogen receptor, and could be induced to produce milk protein. These results demonstrate that human iPSCs can be directed in vitro toward mammary lineage differentiation.

In vitro induction of mammary-like differentiation from human pluripotent stem cells

The invention relates to culturing motor neuron cells together with skeletal muscle cells in a fluidic device under conditions whereby the interaction of these cells mimic the structure and function of the neuromuscular junction (NMJ) providing a NMJ-on-chip. Good viability, formation of myo-fibers and function of skeletal muscle cells on fluidic chips allow for measurements of muscle cell contractions. Embodiments of motor neurons co-cultures with contractile myo-fibers are contemplated for use with modeling diseases affecting NMJ's, e.g. Amyotrophic lateral sclerosis (ALS).

Neuromuscular junction

Efficient method for reprogramming blood to induced pluripotent stem cells

Growing community of inventors

Porter Ranch, CA, United States of America

Dhruv Sareen