Scientists used pluripotent stem cells to generate functional, three-dimensional human stomach tissue in a laboratory — creating an unprecedented tool for researching the development and diseases of an organ central to several public health crises, ranging from cancer to diabetes. Scientists used human pluripotent stem cells — which can become any cell type in the body — to grow a miniature version of the stomach.
The grown tissue will allow researchers to better study illnesses of the stomach, like those that cause ulcers and even cancer. The tissue may even be used as a treatment in and of itself by way of tiny grated patches that would grow over ulcerated stomachs.
The technique could be used within five years or so to create “patches” of tissue to repair ulcers and other stomach damage according to the lead researcher.
Jim Wells, PhD, Divisions of Developmental Biology and Endocrinology at Cincinnati Children’s, explains how the first-time molecular generation of 3D human gastric organoids (hGOs) presents new opportunities for drug discovery, modeling early stages of stomach cancer, studying the underpinnings of obesity related diabetes, and potential tissue regeneration for therapy. Credit: Image courtesy of Cincinnati Children’s Hospital Medical Center
Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world’s population and are largely due to chronic Helicobacter pylori infection. Species differences in embryonic development and architecture of the adult stomach make animal models suboptimal for studying human stomach organogenesis and pathogenesis4, and there is no experimental model of normal human gastric mucosa. Here we report the de novo generation of three-dimensional human gastric tissue in vitro through the directed differentiation of human pluripotent stem cells. We show that temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signalling pathways and three-dimensional growth are sufficient to generate human gastric organoids (hGOs). Developing hGOs progressed through molecular and morphogenetic stages that were nearly identical to the developing antrum of the mouse stomach. Organoids formed primitive gastric gland- and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and a diversity of gastric endocrine cells. We used hGO cultures to identify novel signalling mechanisms that regulate early endoderm patterning and gastric endocrine cell differentiation upstream of the transcription factor NEUROG3. Using hGOs to model pathogenesis of human disease, we found that H. pylori infection resulted in rapid association of the virulence factor CagA with the c-Met receptor, activation of signalling and induction of epithelial proliferation. Together, these studies describe a new and robust in vitro system for elucidating the mechanisms underlying human stomach development and disease.
SOURCES – Science Daily, Nature, Washington Post
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