Tissue engineering and regenerative medicine - our impact
Worldwide 7.9 million children a year are born with serious birth defects and many more develop progressive tissue damage in childhood that does not heal.
This theme builds on expertise in stem cell research and regenerative medicine.
Here you can read about just some of the ways our research theme is already impacting the lives of children.
Pioneering spinal bifida repair before birth in England
In 2018, the first UK prenatal surgeries for spinal bifida (SB) – a malformation where a baby’s spine and spinal cord do not develop properly before birth – were performed by a 30-strong team from GOSH and UCLH, including GOSH researcher Paolo De Coppi.
After demonstrating the procedure’s feasibility and safety, NHS England commissioned two centres to deliver the service: UCLH/GOSH and the University Hospital Leuven, Belgium. So far over 60 patients have been assessed and 25 procedures have taken place. Some of the first patients are starting to see the incredible impact of this treatment.
Babies born with severe SB are often unable to walk, have bowel/bladder incontinence, and need operations to drain fluid from their brain. In the UK SB affects about 700 pregnancies each year. Surgery to close the defect can be carried out soon after birth, but international research demonstrated that performing it before birth decreases mobility problems and other complications.
The operation involves opening the womb to show the defect in the spine, repair it, then closing the womb, without delivering the baby. Previously, mothers-to-be in Britain had to travel abroad for this surgery.
By collaborating with experts in our BRC, the UCLH BRC and the University Hospital Leuven, pooling resources and expertise, we brought this fetal surgery to the UK for the first time.
In 2020, the BBC reported the story of an Essex mother who underwent the surgery by our team in 2019 after being told that her unborn daughter had SB with little chance of being able to walk. Her daughter is now walking and the family say they will ‘forever’ be in debt of staff at both GOSH and UCLH.
BRC funding directly supported development of this service and helped enable its adoption by NHS England. For some babies their SB is too severe for this treatment but for other families it offers an important new option. We expect to perform 15 procedures each year, helping these children grow up with better mobility, fewer health complications and less time in hospital.
BRC funding is now fuelling the next exciting development. Through an international research project (GIFT-Surg), we are developing fetoscopic surgery – operations carried out using tiny 3-4mm incisions that do not need us to open the womb, and so may reduce complications for mother and baby. We have already successfully used this approach in four patients.
Tissue engineering to treat oesophageal atresia
The oesophagus is a multi-layered tube that connects the mouth to the stomach. In oesophageal atresia (OA) the tube ends in a pouch rather than connecting to stomach, meaning the child can’t swallow food. It affects around 240 children each year in the UK. Some have a short gap that is more readily repaired, but 10% have a long gap that needs more complex surgery which is usually delivered at GOSH. Sadly, with current surgical options, one in ten of these children do not survive.
We ran a patient-led international study, working with 11 different European patient support groups to understand what the long-term outcomes for people with OA are. Our investigation highlighted significant long-term effects of surgery where the stomach is moved up into the chest to bypass the missing oesophagus allowing children to swallow.
A potential alternative surgery is to create a tissue engineered oesophagus using the child’s own cells. Tissue engineering offers the prospect of providing new organs for transplantation to repair areas where tissue hasn’t grown properly, or where it has become damaged through illness or trauma, without the need to wait for donor organs. This technique also avoids the risk of organ rejection that occurs with standard transplants as it uses the patient’s own cells. In 2012 and 2015 we reported the successful transplant of a tissue engineered tracheal replacement - the tube that connects your mouth and lungs.
We have now shown that, as well as creating a tissue engineered oesophagus, we can safely store it for two weeks and then, with our collaborators, successfully transplant it in a pre-clinical model. We are now working to develop this approach as a new and real alternative for treatment of oesophageal malformations that children may be born with, or may develop during life.
Our work will have profound implications for children and their families and so we work closely with the two charities, Tracheo-Oesophageal Fistula Support and Esophageal Atresia Global which support families of children unable to swallow. They help ensure the research takes account of patient and family needs. We also work closely with the British Association of Paediatric Surgeons and the MHRA to ensure coordination between regulatory bodies as we work towards the first clinical trial.
To read more:
Outcome of Patients With Esophageal Atresia and Very Low Birth Weight (≤ 1,500 g) - PMC (nih.gov)
Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study - PMC (nih.gov)
Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study - PubMed (nih.gov)
Transplants to treat children without a thymus
The thymus gland produces white blood cells, called T-cells, which play a vital role in fighting infections. Infants born without a thymus are said to have athymia, most commonly due to a rare disorder called complete DiGeorge syndrome (cDGS). As a result, they cannot produce T-cells to fight infections and are likely to die by age two.
In 2021, the 50th patient with athymia was treated at GOSH with a pioneering treatment, transplanting otherwise-discarded thymus tissue into very young children who don’t have a working thymus. The technique uses donated healthy thymus tissue that has been removed from another child during heart surgery – when the thymus tissue needs to be removed to access the heart and would otherwise be discarded. The tissue is then ‘grown’ in the laboratory before implantation into the thigh muscles of the child with athymia.
The hope is the new thymus tissue will create T-cells that restore the child’s immune system. Our BRC work showed that around 75% of patients with cDGS who received a thymus transplant had a successful outcome, developing T-cells and the ability to fight common infections, coming off treatments such as antibiotics and immunoglobulin injections, and were able to attend nursery and school normally.
Recently, research from our BRC Theme has built a functioning thymus from donated human stem cells rather than requiring whole organs or thymus tissues. As well as providing a new source of transplants for children born without a working thymus, this work may impact the future of organ transplantation more widely. As the thymus helps the immune system recognise foreign cells and tissues, it can lead to rejection of an organ transplanted from another person. In the future, we may be able to take cells from the thymus of the organ donor, regrow the thymus and transplant it at the same time as the major organ is transplanted. As the new thymus has come from the same donor as the transplanted organ this could stop the patient rejecting it.
GOSH is the only centre in Europe, one of two worldwide, where children born without a thymus have been transplanted with donor thymi. Now we have successfully carried out this procedure in children, we hope to scale up this work to build human-sized thymi for wider use in patients undergoing organ transplantation to prevent rejection and increase access to organs for transplantation.