In 2012, NIH funded 19 awards for research projects designed to create 3-D chips with living cells and tissues that accurately model the structure and function of human organs, such as the lung, liver and heart. Seven awards explored the potential of stem and progenitor cells to differentiate into multiple cell types that represent the cellular architecture within organ systems. These could act as a source of cells to populate tissue chips.
In addition to organ systems, some of the awarded researchers developed tissue microsystems that target specific health conditions, such as cardiovascular disease, cancer, degenerative arthritis and gastrointestinal disease.
Click on the links below to learn more about the 2012 awarded projects on cell resources:
- Generating Human Intestinal Organoids With an Enteric Nervous System
- Modeling Complex Disease Using Induced Pluripotent Stem Cell-Derived Skin Constructs
- Human Intestinal Organoids: Preclinical Models of Non-Inflammatory Diarrhea
- A 3-D Model of Human Brain Development for Studying Gene/Environment Interactions
- Modeling Oxidative Stress and DNA Damage Using a Gastrointestinal Organotypic Culture System
- Three-Dimensional Osteochondral Micro-Tissue to Model Pathogenesis of Osteoarthritis
- Three-Dimensional Human Lung Model to Study Lung Disease and Formation of Fibrosis
Cincinnati Children’s Hospital Medical Center
Generating Human Intestinal Organoids With an Enteric Nervous System
Principal Investigator: James M. Wells, Ph.D.
Grant Number: 1-U18-TR-000546-01
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.
Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.
Learn more about this project in the NIH RePORTER.
Columbia University Health Sciences, New York
Modeling Complex Disease Using Induced Pluripotent Stem Cell-Derived Skin Constructs
Principal Investigator: Angela Christiano, Ph.D.
Grant Number: 1-U18-TR-000561-01
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.
Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.
Learn more about this project in the NIH RePORTER.
Johns Hopkins University, Baltimore
Human Intestinal Organoids: Preclinical Models of Non-Inflammatory Diarrhea
Principal Investigator: Mark Donowitz, M.D.
Grant Number: 1-U18-TR-000552-01
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 antidiarrheal 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.
Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.
Learn more about this project in the NIH RePORTER.
A 3-D Model of Human Brain Development for Studying Gene/Environment Interactions
Principal Investigator: Thomas Hartung, M.D., Ph.D.
Grant Number: 1-U18-TR-000547-01
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.
Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.
Learn more about this project in the NIH RePORTER.
University of Pennsylvania, Philadelphia
Modeling Oxidative Stress and DNA Damage Using a Gastrointestinal Organotypic Culture System
Principal Investigator: John P. Lynch, M.D., Ph.D.
Grant Number: 1-U18-TR-000536-01
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.
Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.
Learn more about this project in the NIH RePORTER.
University of Pittsburgh
Three-Dimensional Osteochondral Micro-Tissue to Model Pathogenesis of Osteoarthritis
Principal Investigator: Rocky S. Tuan, Ph.D.
Grant Number: 1-U18-TR-000532-01
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.
Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.
Learn more about this project in the NIH RePORTER.
University of Texas Medical Branch at Galveston
Three-Dimensional Human Lung Model to Study Lung Disease and Formation of Fibrosis
Principal Investigator: Joan E. Nichols, Ph.D.
Grant Number: 1-U18-TR-000560-01
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 that 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, that can result from lung infections.
Read a review of this project in the Dec. 20, 2013, issue of Stem Cell Research & Therapy.
Learn more about this project in the NIH RePORTER.
Descriptions are distilled from grant application abstracts.