Houston, Texas, USA : The world’s first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.
It is hoped this research, carried out by UCL Great Ormond Street Institute of Child Health (ICH), in collaboration with Great Ormond Street Hospital (GOSH) and the Francis Crick Institute, could pave the way for clinical trials of lab-grown food pipes for children with congenital and acquired gut conditions.
In the study, published in Nature Communications, researchers used a rat oesophagus “scaffold” and human gut cells to grow engineered tubes of oesophagus. These were implanted into mice and within a week the engineered tissue developed its own blood supply, which is important for a healthy gut that can squeeze down food
Co-lead author, Professor Paulo De Coppi, who is Head of Stem Cells and Regenerative Medicine at ICH and also a Consultant at GOSH, said: “This is a major step forward for regenerative medicine, bringing us ever closer to treatment that goes beyond repairing damaged tissue and offers the possibility of rejection-free organs and tissues for transplant.
“At GOSH we see a large number of referrals for some of the most complex and rare defects of the gut and though the outlook for children is good, the condition and treatments have long-term implications.”
He added: “We’re really excited about these promising preclinical findings. However, lots more research lies ahead before we can safely and effectively translate this approach to humans.”
Future clinical trials could assists the one in 3,000 babies, who are born with a life-changing defect of the gut in the UK each year.
Study co-lead author Dr. Paola Bonfanti, who is Research Associate at ICH and Group Leader at The Francis Crick Institute, said: “This is the first time that such a complicated organ has been grown in the lab.
“Not only is the gut tube shaped, but as it also consists of several different layers of cells, which means we had to use a multi-step approach to develop a piece of oesophagus which resembles and works the same as a normal one. It’s truly a promising step forward for children and even adults with oesophageal conditions.”
Although still in its pre-clinical stage, research into tissue engineering such as this could lead to a new standard of care for patients with complex physical conditions especially in the case of children with damaged organs. The method avoids the need for a donated organ, which are often in short supply for the paediatric population and significantly lowers the risk of organ rejection.
Explore further: Researchers transplant regenerated oesophagus
Citattion: Luca Urbani et al. Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors, Nature Communications (2018). DOI: 10.1038/s41467-018-06385-w
Image credit : Functional engineered oesophagus could pave way for clinical trials. University College London
In a separate earlier study scientists tranplanted a regenerated oesophagus:
Researchers transplant regenerated oesophagus
Tissue engineering has been used to construct natural oesophagi, which in combination with bone marrow stem cells have been safely and effectively transplanted in rats. The study, published in Nature Communications, shows that the transplanted organs remain patent and display regeneration of nerves, muscles, epithelial cells and blood vessels.
The new method has been developed by researchers at Karolinska Institutet in Sweden, within an international collaboration lead by Professor Paolo Macchiarini. 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 oesophagus.
In this new study, the researchers created the bioengineered organs by using oesophagi 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 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 oesophagus 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”, says Paolo Macchiarini, Director of Advanced center for translational regenerative medicine (ACTREM) at Karolinska Institutet.
Tissue engineered organs could improve survival and quality of life for the hundreds of thousands of patients yearly diagnosed with oesophageal disorders such as cancer, congenital anomalies or trauma. Today the patients’ own intestine or stomach is used for esophageal replacements, but satisfactory function rarely achieved. Cultured tissue might eliminate this current need and likely improve surgery-related mortality, morbidity and functional outcome.
Citation : ‘Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats’, 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 & Paolo Macchiarini, Nature Communications DOI: 10.1038/ncomms4562