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A tissue engineering approach to treat defects in the windpipe of babies with fetal stem cells .

Principal investigator: Tina CHOWDHURY
Co-investigator(s): Adrian Hobbs and Paulo De Coppi
Funding source(s): Rosetrees Trust
 Start: 01-10-2015  /  End: 30-09-2018
Directly incurred staff: James Taylor

There is a strong clinical need for tissue replacement in infants and children. Most tissue and organ engineering efforts are targeted at adult patients, who suffer from tissue loss because of injury or disease. However, a substantial number of paediatric patients need surgery to treat defects that are present at the time of birth. Approximately 3% of newborn babies have structural abnormalities that are present at birth and seriously interfere with viability or physical well-being of the young infant. For example, defects in the windpipe or trachea occur in 2% of live births and can cause life-threatening respiratory distress in neonates and infants due to abnormal narrowing of the airways.

 

A possible solution to treating defects in the windpipe is tissue engineering whereby an artificial trachea could be created in the lab with stem cells from the patient. For example, the team at UCL created an artificial trachea in a two year old child using a donor windpipe that was coated with stem cells from the patient’s bone marrow and grew into an organ similar to a healthy one. However, it may be difficult to use this method to treat babies that are born with trachea problems or diagnosed before birth (prenatally) with a complete absence of larynx or trachea, where neonatal surgery is very difficult and use of an artificial material such as prosthesis is often required. In these situations, an artificial trachea could be prepared in the lab before birth using stem cells from the amniotic fluid which surround the developing fetus. There is no need to rely on human donation of the scaffold since the custom-made windpipe could be prepared in the lab and used to treat the baby either before or after birth.

 

In order to be able to transfer tissue engineering techniques into the clinic to benefit babies and infants with congenital trachea malformations, we need to develop methods to define their suitability in paediatrics. The project will use cells derived from the amniotic fluid that could be cultured with fetal progenitors in a bioreactor for the development of tracheal tissues. In previous studies, we showed that the natural, protective protein called C-type natriuretic peptide (CNP) plays a critical role in stem cell differentiation, cartilage growth and repair. In pilot studies, the project team at QMUL and UCL showed that a combination of CNP and growth factors such as TGFb enhanced stem cell differentiation into chondrocytes using cells derived from the amniotic fluid and generated tissues similar to cartilage that are found in the trachea. We will develop ideal cell culture conditions and evaluate the effects of CNP and growth factors on fetal stem cells to produce tracheal tissues in a safe, efficient and effective manner, using a bioreactor system that mimics the environment of the human trachea.

However, the quality of the engineered tissues will be dependent on the type of scaffold used. We will test two types of scaffolds for fetal stem cell differentiation in response to CNP/growth factors and investigate the mechanical strength and flexibility of the newly developed trachea to ensure it matches native tissue. In addition, the growth demands on the material will vary throughout adolescence and therefore our technique will adopt materials that are sensitive to the changes in growth. Functional mechanisms of the tissue-engineered trachea for paediatric organ development will be examined using a combination of mechanical and biological tools previously established at QMUL and UCL.

We believe that the technologies in tissue engineering developed in this project will have great potential for generating functional trachea replacements for babies and infants in the near future.      

The project supports James Taylor during his PhD studentship (2015-2018).