Researchers announced today that tissue engineering has been used to construct natural esophagi - which in combination with bone marrow stem cells - have been safely and effectively transplanted in rats, according to a study published in the prestigious online journal, Nature Communications. The study shows that the transplanted organs remain patent and display regeneration of nerves, muscles, epithelial cells and blood vessels.
The new method was developed by researchers at Karolinska Institutet in Sweden, within an international collaboration lead by Professor Paolo Macchiarini, and including Doris Taylor, MD, Director of Regenerative Medicine Research at the Texas Heart Institute (THI).
“We are very excited and honored to be a part of the team taking such heroic steps, that will ultimately benefit so many patients throughout the world,” said Dr. Taylor, who is leading ground-breaking organ-building work at THI that may ultimately lead to the ability to grow new hearts and other organs using a patient's own stem cells.
Dr. Taylor has collaborated with Professor Macchiarini for several years, and they have jointly published previous papers on tissue engineering. THI and Dr. Taylor are in the midst of multiple international collaborations in this field, and she also serves on a committee named by Texas Medical Center (TMC) President Robert Robbins, MD, to help guide regenerative medicine research throughout TMC.
“The joint goal is to discover, develop, and take first steps toward delivering a more complex tissue, such as a heart,” added Dr. Taylor. “We see this as another important milestone along that path, which we expect will ultimately help many millions of patients.”
James T. Willerson, MD, President, THI added “This is a very important step forward toward the goal of regenerating tissues using Dr. Taylor's methods. The ability to regenerate a patient&'s esophagus after it has been injured, will help many people. The same is true for an injured heart.”
The technique to grow human tissues and organs - so called tissue engineering - has been employed so far to produce urinary bladder, trachea and blood vessels, which have also been used clinically. However, despite several attempts, it has been proven difficult to grow tissue to replace a damaged esophagus.
In this new study, the researchers created the bioengineered organs by soaking esophagi from rats to remove 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 of the recipient. The adhering cells have low immunogenicity, which minimizes the risk of immune reaction and graft rejection and also eliminates the need for immunosuppressive drugs. The cells adhered to the biological scaffold and started to show organ-specific characteristics within three weeks.
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 towards the clinical translation of tissue engineered esophagi,” said Paolo Macchiarini, Director of Advanced Center for Translational Regenerative Medicine (ACTREM) at Karolinska Institutet.
With regard to the esophagus study, tissue engineered organs could improve survival and quality of life for the hundreds of thousands of patients yearly diagnosed with esophageal disorders such as cancer, congenital anomalies or trauma. Today the patients&' own intestine or stomach is used for esophageal replacements, but satisfactory function is rarely achieved. Cultured tissue might eliminate this current need and likely improve surgery-related mortality, morbidity and functional outcome.
The current study was conducted in collaboration with universities in Italy, Russia, Germany and the U.S. It was supported financially by, among others, the Swedish Research Council, the Stockholm County Council through the ALF agreement, and the European Union&'s Seventh Framework Programme. The equipment used in the study was developed by the company Harvard Apparatus Regenerative Technology.
The paper published in Nature Communications is entitled “‘Experimental Orthotopic Transplantation of a Tissue-engineered Oesophagus in Rats.” The paper's authors include Sebastian Sjöqvist, Philipp Jungebluth, Mei Ling Lim, Johannes C. Haag, Ylva Gustafsson, Greg Lemon, Silvia Baiguera, Miguel Angel Burguillos, Costantino Del Gaudio, 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 and Paolo Macchiarini.