A research team led by Paolo Macchiarini, MD, PhD at Karolinska Institutet in Sweden has successfully transplanted a regenerated esophagus into a rat using a bioreactor developed by Harvard Apparatus Regenerative Technology (HART), a spin-off of Harvard Bioscience. Macchiarini has previously done several successful regenerated trachea transplants in human patients using a HART bioreactor.

It has been difficult to grow tissue to replace a damaged esophagus. In humans, an esophagus is much longer and not a hollow tube like a trachea, it is instead muscly. The researchers created the bioengineered organs by using esophagi from rats and removing all the cells. 

With the cells gone, a scaffold remains in which the structure as well as mechanical and chemical properties of the organ are preserved. The produced scaffolds were then reseeded with cells from the bone marrow. The cells adhered to the biological scaffold and started to show organ-specific characteristics within three weeks.

HART-Esophagus regeneration system for use with rat scaffolds. Credit/copyright: Harvard Apparatus Regenerative Technology

The cultured tissues were used to replace segments of the esophagus in rats. All rats survived and after two weeks the researchers found indications of the major components in the regenerated graft: epithelium, muscle cells, blood vessels and nerves.

“We believe that these very promising findings represent major advances toward the clinical translation of tissue engineered esophagi,” said Macchiarini.

David Green, CEO of Harvard Apparatus Regenerative Technology, said, “We congratulate Professor Macchiarini and his research team for this breakthrough in the development of a regenerated esophagus for transplant. We are honored to have been able to support this work by adapting our trachea regeneration bioreactor specifically for the regeneration of the esophagus. We look forward to continuing our collaboration with Professor Macchiarini in developing this technology with the goal of performing the first human transplant of a regenerated esophagus.”

This research will be presented next week at the American Association for Thoracic Surgery (AATS) Annual Meeting 2014 in Toronto.

Citation: Sebastian Sjöqvist, Philipp Jungebluth, Mei Ling Lim, Johannes C. Haag, Ylva Gustafsson, Greg Lemon, Silvia Baiguera, Miguel Angel Burguillos, Costantino Del Gaudio, Antonio Beltrán Rodríguez, Alexander Sotnichenko, Karolina Kublickiene, Henrik Ullman, Heike Kielstein, Peter Damberg, Alessandra Bianco, Rainer Heuchel, Ying Zhao, Domenico Ribatti, Cristián Ibarra, Bertrand Joseph, Doris A. Taylor, Paolo Macchiarini, 'Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats', Nature Communications, 15 April 2014 doi:10.1038/ncomms4562