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Generation and characterisation of progenitor cell lines from human fetal kidneys

Mari, Chiara; (2018) Generation and characterisation of progenitor cell lines from human fetal kidneys. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Kidney disease is a global public health burden. Chronic kidney disease, with an incidence increasing annually in the Western world, is a progressive kidney damage that can lead to end-stage renal failure (CKD5), in which kidney function is completely lost. CKD5 treatment options are dialysis, which is not a cure for kidney disease and kidney transplantation limited by the shortage of donor organs. Kidney disease new interventions have two aims: 1. preventing the progression to CKD5 2. creating a healthy organ in vitro with bioengineered scaffolds in order to permanently replace defective kidneys. The first aim involves the utilisation of drug- and cellular- based therapies to delay or to stop the progression to CKD5. However, this aim is made problematic by the paucity of available primary human renal cell lines to be used for new drugs testing and the incapability to accurately assess the efficacy of cellular-based therapies in appropriate animal models. The PhD Thesis illustrates the attempt in meeting this need. The thesis focuses on the generation and characterisation of human progenitor cell lines and further assessment of their potential to be used as cell-based therapy. I have generated human fetal cell lines from healthy kidneys, based on the expression of known markers of renal progenitor cells, CD24 and CD133. I have characterised their gene expression profile over multiple passages, assessing the expression of progenitor and lineage markers and evaluated their capacity to differentiate towards multiple lineages (osteoblasts, adipocytes and renal epithelia). Furthermore, the potential of these cells to be used as therapy has been assessed in mouse model of acute renal injury induced by folic acid after comparing the course of the folic acid-induced renal injury in immunocompetent and immunodeficient mice strains.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Generation and characterisation of progenitor cell lines from human fetal kidneys
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity.
UCL classification: UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10050589
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