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Title: Identifying the optimal stem cell populations for vascular tissue regeneration used in paediatric congenital heart surgery
Author: Jia, Huidong
ISNI:       0000 0004 5917 1138
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Congenital heart disease (CHO) affects 1 % of live births, and remains the primary cause of death among infants in North America and Europe. In congenital heart defect corrective surgery, the commonly used prosthetic replacement grafts have limited durability and often require repeat operations because of their lack of growth potential. Using the child's autologous stem cells to produce tissue engineered vascular grafts holds promise for the creation of living grafts for surgery. It is therefore essential to identify a readily available autologous stem cell source that is able to produce sufficient functional endothelial cells (ECs) and vascular smooth muscle cells (SMCs) for vascular tissue regeneration. Human endothelial progenitor cells (UCB-EPCs) and mesenchymal stem cells (UCBMSCs) were isolated from umbilical cord blood by density gradient centrifugation and selective medium incubation. Meanwhile, another type of multipotent stem cells (WJPVCs) were isolated from perivascular regions among the umbilical cord by outgrowth methods. Functional EC were derived from UCB-EPCs and characterised by their surface markers and angiogenesis assay. UCB-MSCs and WJPVCs were induced by TGF-β1 to differentiate into SMC like cells, which also obtained a similar SMC phenotype. These matured cells showed great cell-matrix compatibility, satisfactory proliferative ability, when seeded onto a decellularised scaffold. Porcine EPCs and MSCs were isolated from newborn piglet peripheral blood by a similar methodology derived human UCB-EPCs and UCB-MSCs. The matured vascular cells derived from these porcine stem cells were applied in constructing a dual cell seeded tissue engineered conduit. The graft was implanted into the left pulmonary of a 30kg weight piglet, and then harvested 3 months later. Immunohistological tests revealed that the graft had a good patency, had been well integrated with adjacent artery tissues and was able to form natural-artery like structure, including endothelium and media SMC-like layers. These results revealed that perinatal tissue is a viable readily available source of autologous stem cells for use in generating living tissue engineered vascular graft for paediatric congenital heart surgery.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available