Tissue Engineering of Lung and Gut Sections

The first practical outcome of tissue engineering research is not therapies, but rather improved tools for further scientific work in this and other fields. At present the structured tissue sections created in the laboratory are largely too small or too dissimilar from natural organs for use in treatments, but these engineered tissues can nonetheless be very useful in drug testing, investigation of disease mechanisms, and many other aspects of medical research. Real tissue is a vast improvement over cells in a dish and animal models, and real tissue grown from patient cells is a tremendous step forward for work on genetic disorders. In the economic development of the field, the ability for companies to form and make money by providing these tools is a vital stepping stone on the way to improving the underlying technologies. That will lead in time to building whole organs to order, one step at a time.

Scientists grow 'mini-lungs' to aid the study of cystic fibrosis

Scientists have successfully created 'mini-lungs' using stem cells derived from skin cells of patients with cystic fibrosis, and have shown that these can be used to test potential new drugs for this debilitating lung disease. The research is one of a number of studies that have used stem cells - the body's master cells - to grow 'organoids', 3D clusters of cells that mimic the behaviour and function of specific organs within the body. Researchers used skin cells from patients with the most common form of cystic fibrosis caused by a mutation in the CFTR gene referred to as the delta-F508 mutation. Approximately three in four cystic fibrosis patients in the UK have this particular mutation. They then reprogrammed the skin cells to an induced pluripotent state, the state at which the cells can develop into any type of cell within the body.

Using these induced pluripotent stem cells, or iPS cells, the researchers were able to recreate embryonic lung development in the lab by activating a process known as gastrulation, in which the cells form distinct layers including the endoderm and then the foregut, from which the lung 'grows', and then pushed these cells further to develop into distal airway tissue. The distal airway is the part of the lung responsible for gas exchange and is often implicated in disease, such as cystic fibrosis, some forms of lung cancer and emphysema. "In a sense, what we've created are 'mini-lungs'. While they only represent the distal part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice. We can use them to learn more about key aspects of serious diseases - in our case, cystic fibrosis. We're confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis. This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research."

Researchers seek to make mini-guts that mimic life

"We are already making human mini-guts in the laboratory. We make them, we can freeze them." However, they are not a perfect model, and she hopes this project will result in better ones. Not only will they have the stretch and pull of living guts, but will also include the immune cells found underneath the epithelium of the gut and the mesenchymal and nerve cells that enhance the environment and function of the gut.

There are two major projects. Project one uses human intestinal enteroids (cells taken from the gastrointestinal tract) to analyze how those cell react to human rotavirus and vaccine replication as well as enteroaggreative E. coli, defining how the epithelial cell responses lead to pathology or disease. Project two will combine tissue engineering, biomaterial design and mechanobiology to develop specially tailored platforms for the human intestinal enteroids that can be stimulated mechanically, promoting cell and tissue polarity and differentiation of intestinal tissue to facilitate infection with the rotaviruses and E. coli. "Infectious disease labs that study enteric disease need better models that faithfully simulate the physiology of the intestine. This organ contains multiple types of cells that are arranged in complex patterns, and these tissues are constantly on the move. They contract and expand all the time."

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