bio-engineered oesophagus

Scientists in London have grown a bio-engineered oesophagus which was successfully implanted into mice.

A tissue-engineered oesophagus could overcome limitations associated with oesophageal substitution. Combining decellularized scaffolds with patient-derived cells shows promise for regeneration of tissue defects. In this proof-of-principle study, a two-stage approach for generation of a bio-artificial oesophageal graft addresses some major challenges in organ engineering, namely: (i) development of multi-strata tubular structures, (ii) appropriate re-population/maturation of constructs before transplantation, (iii) cryopreservation of bio-engineered organs and (iv) in vivo pre-vascularization.

Oct 16th, 2018

Lab-grown oesophagus

Scientists at UCL Great Ormond Street Institute of Child Health (ICH), Great Ormond Street Hospital (GOSH) and the Francis Crick Institute.

The team hopes the research could eventually lead to clinical trials of lab-grown food pipes for children born with part of their oesophagus damaged or missing.

The oesophagus is a complex, multi-layered organ, made up of multiple tissue types, which acts as a pipe carrying food and liquid from the mouth to the stomach.

The team used a rat oesophagus, which was stripped of its cells, leaving behind a collagen scaffold.

They seeded it with early-stage muscle and connective tissue from mice and humans, and other early rat cells which went on to form the lining on the inside of the organ.

The use of stem cells from different species enabled researchers to differentiate between the origin of each tissue type which developed.

The 2cm sections of oesophagus were implanted into the abdomen of mice.

Dr Paola Bonfanti, co-author and group leader at the Francis Crick Institute and UCL Great Ormond Street Hospital Institute of Child Health (ICH), said: “We were amazed to see that our engineered tissue had both the structure and function of a healthy oesophagus, and hooked up with nearby blood vessels within a week of transplantation.”

The sections of oesophagus were capable of muscle contraction, which is needed to move food down to the stomach.

Around one in 3,000 babies is born with abnormalities of the oesophagus, usually involving a gap between the upper and lower section, or where it does not connect with the stomach.

Someone in our group we run via this website asked this question, (Does anyone know why they don’t do donor esophagus?) my reply was (size might play a part) Prof Paola De Coppi then replyed (Paolo De Coppi Correct Steve. Thank you for being interested in the approach. Our group has already transplanted some tissue engineering trachea to patients but we failed to find donors fro neonate with this problem. Once the cells are stripped out, the pig oesophagus is very similar to the human one. Pig tissue is already often used in human (i.e. cardiac valves)

Paolo De Coppi Thank you all for being interest on the research. Of course, we are doing more studies to understand but there is no need of antirejection drugs on this system. The pig oesophagus is used only as a scaffold an the cells are the patient’s ones.

Prof Paolo De Coppi, co-author and consultant surgeon at Gosh, and head of stem cells and regenerative medicine at ICH, 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.”

There are several years of research required before this might be ready for clinical use, including more animal trials, involving larger mammals.

The eventual aim would be to create bio-engineered organs from a pig oesophagus, which would be injected with a patient’s own stem cells, in order to minimise the risk of rejection.

Hudson Wakelin, aged two, was born without part of his oesophagus.

He has had surgery at Gosh to lift his stomach up into his chest in order to connect it directly to his throat.

It now means he can eat some of the same meals as his twin, Hank, but needs careful eating support to ensure food does not get into his windpipe.

His mum, Nicola, said: “Hudson has to eat little and often. We have to be careful that he doesn’t choke, and he suffers from reflux, bringing up food and stomach acid, which can create problems.”

Nearly 250 children a year are born in the UK with Hudson’s condition, known as oesophageal atresia, and the research is aimed at helping those where current surgical options bring limited benefits.

The field of engineered organ transplants suffered a major setback in 2016 when a surgeon in Sweden, Paolo Macchiarini, was accused of falsifying his science.

Of nine patients who received a synthetic windpipe, seven died, and the two survivors had the organ replaced with a donor trachea.

The team at the Crick and Gosh say the scandal reinforced their determination to proceed cautiously.

https://www.bbc.co.uk/news/health-45838421

Lab-grown oesophagus

This is taken from the full report above, the link shown on banner holds a lot of info, drawings, etc for what made the News around the World on Oct 16th, 2018.

In summary, with the present study, we reconstructed a layered full-circumferential oesophageal tissue in vitro and propose its future use as a potential alternative treatment for oesophageal atresia or other oesophageal defects, where tissue replacement is needed. The approach here described could be easily scaled-up to larger constructs in the view of future pre-clinical experiments in larger animal models where all components are human.

Paolo De Coppi

  • Stem Cell and Regenerative Medicine Section, Great Ormond Street Institute of Child Health, University College of London, London, WC1N 1EH, UK
  • Specialist Neonatal and Paediatric Unit, Great Ormond Street Hospital, London, WC1N 1EH, UK

15 July 2014

Plans to open the world’s first centre dedicated to paediatric research into rare diseases at Great Ormond Street Hospital (GOSH) are to become a reality thanks to a £60 million gift from Her Highness Sheikha Fatima bint Mubarak.

The gift, given by the wife of the late Sheikh Zayed bin Sultan Al Nahyan, founder of the United Arab Emirates, is in recognition of GOSH’s unique position to advance treatments and cures in this area. It builds on the legacy of her late husband who had an active interest in global issues affecting the wellbeing of children. It is also given in gratitude to the hospital for the pioneering treatments it has provided to children from around the world, including those from the UAE.

The centre is a partnership between GOSH, University College London (UCL) and the Great Ormond Street Hospital Children’s Charity. The building, whose site is adjacent to the hospital and the UCL Institute Child Health, is set to bring hundreds of clinicians and researchers together where they will see patients and access state-of-the-art laboratory facilities under one roof.

Rare diseases represent a considerable health burden globally as taken together they affect one in 17 people at some stage of their lives. They are particularly prevalent in children and nearly one third of the children affected will die before their fifth birthday. GOSH and UCL are uniquely placed to translate groundbreaking research into better treatments and cures as together they have more dedicated paediatric researchers into rare disease and see more children with rare diseases than anywhere else in the world.

Her Highness Sheikha Fatima bint Mubarak said: “The most important work that we can undertake as a global society is to improve the health of future generations so that communities can thrive and grow. To reach this goal, we must form collaborative partnerships that have the potential to benefit all children. We are honored to support the mission and work of Great Ormond Street Hospital.”

Baroness Blackstone, chair of Great Ormond Street Hospital said: “This gift is truly transformative and we are incredibly grateful. There is an urgent and compelling case to use our expertise and harness the recent advances in science and technology to accelerate the discovery of new treatments and cures in this area.

“This facility will be a center of excellence for translational research and a beacon of hope for children with rare diseases around the world.”

Professor Michael Arthur, University College London President, and Provost, said: “In recent years GOSH and UCL have achieved some amazing breakthroughs in the treatment of rare diseases and it is without question the partnership between academic science and clinical medicine that has made the progress possible.

“This state-of-the-art centre will enable a step change in research. In particular it will drive our experts to progress new and personalised ways to diagnose and treat these children by further developing gene and cell therapies and manufacturing increasingly complex medical devices.”

Representing Her Highness Sheikha Fatima bint Mubarak, Her Excellency Professor Maha Barakat will visit Great Ormond Street Hospital today to mark the announcement. On her visit she will meet some of the patients that could benefit from the research that will be undertaken in the new centre.

Her Excellency Professor Maha Barakat said: “For more than 160 years, Great Ormond Street Hospital has provided children with the medical care they have needed, and this new centre will be an extension of this essential work. We are indebted to the people of Great Ormond Street Hospital who dedicate themselves to helping thousands of children every year who are suffering from life-threatening and life-limiting conditions.”

The centre will be built on a plot of land on Guilford Street. The award-winning architects Stanton Williams are working with the clinical and academic staff to create a high quality building with outstanding research and clinical facilities. Currently the first phase of the public consultation process is underway, with the centre expected to open in 2018.

It is anticipated that the centre will house approximately 400 academics and clinical staff and feature more than 150 laboratory bench positions. The outpatients’ facility will accommodate 48 clinical staff, and 140 patients with accompanying family members.

The total cost of the centre is expected to be £90 million. The full cost has been met by £20 million of fundraising income from Great Ormond Street Hospital Children’s Charity and a £10 million grant from the Higher Education Funding Council for England’s Research Partnership Investment Fund.

Her Highness Sheikha Fatima bint Mubarak is the wife of the Founder and the First President of the United Arab Emirates, the late Sheikh Zayed bin Sultan Al Nahyan. Known as the ‘Mother of the Nation’, Her Highness Sheikha Fatima is recognised globally for her support of charitable work and humanitarian projects.

Her Highness is a leading figure in supporting initiatives and projects to empower women locally, regionally and internationally. Her Highness Sheikha Fatima is also known for her focus on family and children.

The Legacy of the late Sheikh Zayed bin Sultan Al Nahyan

Sheikh Zayed bin Sultan Al Nahyan, Ruler of Abu Dhabi from 1966 to 2004 and First President of the United Arab Emirates from 1971 to 2004, is widely recognised as the ‘Father of the Nation’. He established bodies including the Zayed Charitable and Humanitarian Foundation and the Abu Dhabi Fund for Development, as well as institutions like the Red Crescent Society.

One of the first to join the international campaign against Guinea worm disease, the late Sheikh Zayed bin Sultan Al Nahyan, Founding Father of the United Arab Emirates, invested significant resources in the 1990s to help launch the Guinea Worm Eradication Program. This early investment enabled the program, based at the Carter Center, to establish global operations and accelerate interventions against Guinea worm disease.

Continuing the work of the late Sheikh Zayed bin Sultan Al Nahyan, in 2012, His Highness Sheikh Khalifa bin Zayed Al Nahyan, President of the UAE, pledged US$10 million towards the vision of ending Guinea worm disease by 2015. Led by the Carter Center and supported by two other main donors: Bill & Melinda Gates Foundation; and the Children’s Investment Fund Foundation, together, the three donors provided a total of US $40 million.

In 2009 the Sheikh Zayed Institute for Pediatric Surgical Innovation was established at the National Medical Center in Washington DC after a $150million gift from Abu Dhabi. The gift followed a longtime relationship between the hospital and the United Arab Emirates, and reflects a shared vision to advance medical innovation to improve children’s health worldwide.