A tissue engineered oesophagus that can resist mechanical stress and is functional when implanted in to a rat, is reported in Nature Communications. This work could represent an important step towards the development of clinically successful bioengineered oesophageal replacements.
Every year a large number of individuals undergo surgical procedures to remove sections of oesophagus in response to oesophageal cancer, traumatic disorders or birth defects that affect the digestive tract. While a variety of surgical options are available to restore digestive function, most procedures are complex and associated with substantial complications, weight loss and mortality. An approach that uses bioengineered tissues to replace damaged segments would, in theory, avoid high-risk surgeries, be readily available, reduce side effects and improve long-term functional outcome.
In the first steps towards this, Paolo Macchiarini and colleagues stripped cells from a section of oesophagus in a rat model in order to create a biocompatible scaffold that retained mechanical and bioactive properties of the organ. This scaffold was then re-seeded with rat bone marrow mesenchymal stromal cells. A segment of the original oesophagus, representing 20% of the total length, could then be removed and replaced with the engineered, re-seeded graft in the living rat.
Post procedure, the team monitored the rats over a two-week period and, although the rats were initially immobile, the researchers noted that they quickly recovered and did not show any significant signs of pain or health impairment, organ rejection or adverse immunological responses. Additionally, several newly developed blood vessels and muscle fibres were found in the graft. Using a liquid and soft food diet post-surgery also led to notable weight gain in the animals when compared to a control group.
While the authors caution that the transplantation of only 20% of oesophageal length shown in this study might not be clinical useful and the functionality of the implant over longer periods of time remains to be demonstrated, the feasibility of this type of approach in smaller animals and over shorter time scales is promising and paves the way for evaluation in for larger animal models where total oesophageal replacement and longer follow-up may be possible.