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Development of an engineered lung tissue from human induced pluripotent stem cells and acellular matrix using a newly designed bioreactor

Tommasini, Fabio; (2018) Development of an engineered lung tissue from human induced pluripotent stem cells and acellular matrix using a newly designed bioreactor. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The number of deaths around the globe due to lung diseases is over 9.5 million each year, including the paediatric population, and it is expected to increase. Currently the only treatment for many end-stage debilitating lung diseases is orthotopic lung transplantation. Nonetheless, there are several problems associated with this procedure, including shortage of donor organs, the risk of allograft rejection, organ failure and the lifelong burdening regimen of immunosuppressive drugs that the patients must take. One potential solution is the transplantation of a bioengineered lung made from patient’s own cells. With this approach, damaged or immunologically incompatible lungs of allogeneic or xenogeneic origin can be decellularised to generate scaffolds that retain the macro/micro architecture and topological specificity, including a perfusable vascular bed. These acellular scaffolds could be then seeded with patient specific cells of epithelial and endothelial origin and transplanted back to the patient. In this project, human amniotic fluid stem cells (hAFSC) were reprogrammed into induced pluripotent stem cells (iPSC) using clinically relevant episomes, and cell lines were thoroughly characterised. The potential of the iPSC to be directly differentiated into endodermal and mesodermal lineages such as the alveolar epithelium and vasculature respectively was then assessed. In parallel, a novel automatic decellularisation/recellularisation bioreactor was designed in which the aforementioned cells were seeded and cultured, under dynamic conditions. The combination of the acellular constructs, the lung epithelial cells from iPSC as well as vascular cells all put together represents a proof of concept towards the translation of tissue engineered lungs to the clinics.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Development of an engineered lung tissue from human induced pluripotent stem cells and acellular matrix using a newly designed bioreactor
Event: UCL (University College London)
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10054043
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