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25 Mar 2015

Cambridge Scientists Created Mini Lungs from Stem Cells

The researchers at Cambridge University have successfully created lab grown Mini Lungs from stem cells to study the effects of cystic fibrosis and its treatment options.

Generally, scientists use lab grown animal models to test new therapies or screen drugs that can be used to treat serious medical conditions in humans. Often these models do not give conclusive results as the drug might either work effectively on animal models but pose adverse side effects on humans or shows ineffectiveness in mice model but have the potential to cure humans. This inconsistency in drug trials and clinical research leads to delayed therapy, increased research costs etc.

Organoids – Human Models to Aid in Research

To avoid such delays, scientists have created realistic models of human tissue called ‘organoids’ using modified stem cells. Stem cells have the ability to grow and differentiate into any type of cell in the body, thus they are perfect to create any desired mini-organ or organoids for research trials. Earlier reports show that scientists have created organoids of human intestine and pancreas to study the working of diseases and effectiveness of new drugs. Recently, the Cambridge researchers have created mini-lungs using stem cells and tested a new therapy to treat cystic fibrosis, a lung disease that affects humans.

Cystic Fibrosis – How is it Formed?

Cystic fibrosis is a genetic disease characterized by breathing difficulty, chronic illness, frequent lung infection, poor growth etc. This is a condition in which the lungs produce too much thick mucus that results in breathing problems and infection in the respiratory tract. It is caused by a single gene mutation observed in CFTR gene, called as delta-F508 mutation. In patients with delta-F508 mutation, the protein expressed from CFTR gene does not fold correctly in the airway tissue, thereby causing improper expression on the cell surfaces. This affects the chloride channels responsible for the movement of chloride ions in and out of the cells present in the airway tissue. This in turn results in restricted water movement to the linings of the lungs which cause sticky mucus.

As the mucus becomes too sticky, it results in breathing difficulties, high risk of bacterial infection and even leads to fibrosis or scarring.

Mini Lungs Replicate the Cystic Fibrosis Environment

The scientists from Cambridge used the stem cells from the skin of cystic fibrosis patients to generate organoid models of the distal part of lung tissue. The study leader, Nick Hannan mentioned that this model is more reliable than the traditional animal models and can be used to study the key aspects of serious illnesses such as cystic fibrosis.

During the research, the skin cells with delta-F508 mutation are reprogrammed to form induced pluripotent stem cells which have the potential to form any kind of cells. Through a process similar to gastrulation (differentiation of embryo to form various tissue type), the scientists recreated the lung tissue from induced pluripotent stem cells which mimics the conditions that would exist in an actual cystic fibrosis tissue.

To test the effectiveness of the mini lungs, the scientists used a fluorescent dye which is sensitive to chlorides. Using the dye system, it was evident that the cells in the mini lungs have restricted chloride movement when compared to healthy cells. The team also demonstrated how adding a small molecule helped in the easy movement of chloride ions in the organoid system.

Volution of Stem Cell Research

“We're confident this process could be scaled up to enable us to screen tens of thousands of compounds… This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research", Dr. Hannan added.

Stem cells were initially used for therapeutic purposes in the medical world but in the present day research, these potential life savers have evolved to help in the testing of new drugs and new therapies. The scope of stem cells are widening every day with more useful applications for mankind. However, the best part is that they come from adult body cells and cause no ethical challenge like embryonic stem cell research.



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