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Tissue engineering using stem cells and potential application in the correction of congenital heart defects


About This PhD Project

Project Description

Congenital heart defects (CHD) are the primary cause of infant deaths In Europe and North America. Surgery is the primary
treatment for CHD but the major problem with surgery for such defects is the lack of living replacement
materials with the capacity to grow and remodel. Many children need prosthetic replacement grafts in the form of
new valves, conduits and patches, however although these grafts may be life saving, they have limited durability and
often require repeat operations in the future. Due to the lack of growth potential of the currently available grafts, a child
born with congenital heart defects may typically need to undergo major cardiac surgery several times throughout their lifetime. We believe that with the use of stem cells we will be able to devise a graft that will grow with the patient, thereby eradicating the need for additional cardiac surgery. This project investigates the use of perinatal derived stem cells for tissue engineering grafts. Stem cells will be isolated, expanded and characterized then seeded onto different scaffolds and grown in a bioreactor. The resulting seeded graft will be investigated for morphology changes and cardiovascular cell markers’ expression using electron scanning microscopy, immunohistochemistry and RT-realtime PCR. Additionally, the seeded graft will be assessed for biomechanical and contractility properties. Furthermore, the tissue-engineered graft will be implanted into a piglet model and its durability, growth potential and suitability to corrective heart surgery will be assessed. This work should pave the way to the human trial.

When applying please select ’Medicine PhD’ within the Faculty of Health Sciences.

References

Mao AS, Mooney DJ. Regenerative medicine: Current therapies and future directions. PNAS 2015;112:14452-14459.
Jia H, Caputo M, Ghorbel MT. Stem cells in vascular graft tissue engineering for congenital heart surgery. Interv. Cardiol 2013; 5(6): 647–662.
Cebotari S, Lichtenberg A, Tudorache I, Hilfiker A, Mertsching H, Leyh R et al. Clinical application of tissue engineered human heart valves using autologous progenitor cells. Circulation 2006;114:132-137.
Pillekamp F, Reppel M, Brockmeier K, Hescheler J. Stem cells and their potential relevance to paediatric cardiology. Cardiol Young 2006;16:117-124.

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