Small Steps Towards Tissue Engineered Lungs

From a starting point of a few cells, researchers can at present build small amounts of at least partially functional tissue for a range of organs, including lungs. These are known as organoids, limited in size because reliable methods of generating the blood vessel networks needed to support larger tissues have yet to be developed. For some organs, those that largely act as filters or chemical factories, it is possible that organoids alone can have significant therapeutic value: transplant many of them at once and let them integrate into a damaged organ to augment its function, for example. For organs like the lung, however, where overall structure is important, there is further to go. The leap must be made from organoids to, at minimum, large and properly structured tissue sections. Meanwhile, the existence of organoids does allow researchers to gain valuable experience in tissue engineering, and to refine the outcomes achieved to date. That is important. This is a journey of many small steps:

Researchers have transplanted lab-grown mini lungs into immunosuppressed mice where the structures were able to survive, grow and mature. "In many ways, the transplanted mini lungs were indistinguishable from human adult tissue." Respiratory diseases account for nearly 1 in 5 deaths worldwide, and lung cancer survival rates remain poor despite numerous therapeutic advances during the past 30 years. The numbers highlight the need for new, physiologically relevant models for translational lung research. Lab-grown lungs can help because they provide a human model to screen drugs, understand gene function, generate transplantable tissue and study complex human diseases, such as asthma.

Researchers used numerous signaling pathways involved with cell growth and organ formation to coax stem cells - the body's master cells - to make the miniature lungs. The researchers' previous study showed mini lungs grown in a dish consisted of structures that exemplified both the airways that move air in and out of the body, known as bronchi, and the small lung sacs called alveoli, which are critical to gas exchange during breathing. But to overcome the immature and disorganized structure, the researchers attempted to transplant the miniature lungs into mice, an approach that has been widely adopted in the stem cell field. Several initial strategies to transplant the mini lungs into mice were unsuccessful.

The team used a biodegradable scaffold, which had been developed for transplanting tissue into animals, to achieve successful transplantation of the mini lungs into mice. The scaffold provided a stiff structure to help the airway reach maturity. "In just eight weeks, the resulting transplanted tissue had impressive tube-shaped airway structures similar to the adult lung airways." Researchers characterized the transplanted mini lungs as well-developed tissue that possessed a highly organized epithelial layer lining the lungs. One drawback was that the alveolar cell types did not grow in the transplants. Still, several specialized lung cell types were present, including mucus-producing cells, multiciliated cells and stem cells found in the adult lung.

Link: http://www.newswise.com/articles/lab-grown-mini-lungs-successfully-transplanted-into-mice2

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