Researchers may have successfully engineered functional esophagi that resist stress, staying open and unobstructed after they were implanted into living rats.
People suffering from esophageal cancer, as well as certain traumas and birth defects, often undergo surgery to remove damaged sections of their esophagus. Many post-surgery options to restore their digestive function exist -- such as creating replacement parts from the patient’s own intestine or stomach -- but these come with serious complications.
For a way to avoid additional surgeries and reduce side effects, an international team led by Paolo Macchiarini of Karolinska Institutet in Stockholm tried to construct a readily available, natural replacement esophagus. While tissue engineering has been used to create bladders, trachea, and blood vessels, several attempts at a replacement esophagus have failed thus far.
So, in order to maintain the mechanical and biochemical properties of the organ, they started by stripping cells from a section of esophagus in rats to create an empty yet biocompatible scaffold. Pictured below, the “decellularized” esophagus inside a perfusion chamber after 100 minutes of decellularization. To make sure it could withstand mechanical stress, the team pumped air into it 10,000 times, blowing it up and deflating it back down.
The scaffold was then seeded with stem cells harvested from the rats’ own bone marrow, called mesenchymal stromal cells. Within three weeks, the cells on the scaffold spontaneously differentiated into various esophageal cells, showing organ-specific characteristics. “We were really surprised at the level of differentiation we got," Macchiarini tells Live Science.
They removed a segment of the rats’ original esophagi -- about 20 percent of their total length -- and replaced them with the bioengineered, re-seeded graft in the living rats. All the rodents survived the surgery, recovering over the course of a couple weeks. A liquid and soft food diet helped with their weight gain.
None of the rats showed any signs of health problems or immune responses -- since using their own cells helps minimize the risk of graft rejection. In fact, epithelial cells, nerves, blood vessels, and muscle fibers started to regenerate in the implanted material. But of course, longer-term follow up with larger animal models, as well as longer sections of esophagi, will be needed before this method becomes clinically useful.
The work was published in Nature Communications this week.
Images: Macchiarini et al.