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Tissue Chip Awards: Cell Resources

Cincinnati Children’s Hospital Medical Center

Generating human intestinal organoids with an enteric nervous system
James M. Wells, Ph.D.

Gastrointestinal motility/functional disorders affect up to 25 percent of the U.S. population, but few drugs target the primary deficiencies in controlled peristalsis, the muscle contractions that transport food and waste through the body’s digestive tract. This project aims to generate human intestinal organoids containing functional epithelium, surrounded by smooth muscle innervated by enteric nerves to allow for cellular and molecular gut motility studies in humans and serve as a screening platform for drugs that regulate motility.

Columbia University Health Sciences, New York City

Modeling complex disease using induced pluripotent stem cell-derived skin constructs
Angela Christiano, Ph.D.

This proposal aims to establish a skin construct composed entirely of fibroblasts and keratinocytes derived from induced pluripotent stem cells (iPSCs), to produce an unlimited supply of disease-specific donor cells for use in skin constructs, which can be differentiated into multiple cell lineages. This platform can be expanded to generate models of other complex skin disorders for which new therapeutic options are in great demand.

Johns Hopkins University, Baltimore

Human intestinal organoids: Pre-clinical models of non-inflammatory diarrhea
Mark Donowitz, M.D.

Researchers need an available and easy-to-use model of the human intestine to better understand human intestinal physiology, pathophysiology of diarrheal diseases and how to develop anti-diarrheal drug therapy. This project will compare two types of human small intestinal organoids to advance understanding in several diarrheal diseases, including cholera, rotavirus and enterohemorrhagic E. coli.

Johns Hopkins University, Baltimore

A 3-D model of human brain development for studying gene/environment interactions
Thomas Hartung, M.D., Ph.D.

A 3-D rat mini brain model successfully used for developmental neurotoxicity testing will be humanized using induced pluripotent stem cells. Using cells from healthy donors and patients, researchers will be able to study for the first time gene/environment interactions. This model has the potential to replace animal testing with a more predictive human model.

University of Pennsylvania, Philadelphia

Modeling oxidative stress and DNA damage using a gastrointestinal organotypic culture system
John P. Lynch, M.D., Ph.D.

Long-term consequences of chronic inflammatory conditions (e.g., gastroesophageal reflux disease) can include metaplasia and cancer. Presently, little is known about how these conditions develop in the setting of chronic inflammation. This proposal describes approaches to model and mechanistically explore the contributions of Cox-2, oxidative stress and DNA damage, inflammatory cells, and epithelial cells to the pathogenesis of metaplasia and cancer. Project investigators anticipate that these approaches will yield improved human cell culture models suitable for testing and novel therapeutic and preventive strategies that will improve patient care for these important clinical conditions.

University of Pittsburgh

Three-dimensional osteochondral micro-tissue to model pathogenesis of osteoarthritis
Rocky S. Tuan, Ph.D.

Osteoarthritis, a degenerative joint disease that affects up to 15 percent of adults, is initiated by degeneration of the articular cartilage that covers the joint surface. Development of disease-modifying osteoarthritis drugs requires a clear understanding of the underlying mechanisms, responsible for the failed interaction between cartilage and bone. This proposal aims to establish an in vitro 3-D microsystem based on adult stem cells to simulate this bone-cartilage interface, which may be used in the future to identify and test candidate therapeutics for osteoarthritis.

The University of Texas Medical Branch at Galveston

Three-dimensional human lung model to study lung disease and formation of fibrosis
Joan E. Nichols, Ph.D.

A human 3-D organ model composed of native cell types interacting in a physiologically relevant way may more closely approximate in vivo conditions. Development of improved in vitro organ models would enable researchers to construct and analyze complex biological systems especially as they relate to organ development, disease pathogenesis, toxicology and drug discovery.

This project aims to develop engineered human lung tissue to use as a model. The model will be grown using human stem cells, human derived cell lines or primary cells seeded onto small pieces of scaffold which will support 3-D tissue development. These tissue pieces will share many of the cell types found in the lung and will be used to study lung development, microbial lung infections and diseases such as fibrosis which can result from lung infections.

Descriptions are distilled from grant application abstracts.

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