Human organoids as a powerful emerging technology for the study of ageing
Ingham Institute for Applied Medical Research UNSW Sydney, Sydney, New South Wales, Australia
Ageing is widely believed to be a consequence of accumulating cellular damage over time; yet studying this damage in humans represents a significant technical challenge. Genetically modified animal models while informative, only approximate the physiological context of ageing in human cells and 2D cell cultures are either artificially immortalised or disadvantaged by dedifferentiation and genetic drift. Human organoids are a powerful emerging technology for studying human disease and have the potential to effectively balance the strength and weaknesses of the traditional models of ageing. A 3D Organoid cell culture is a self-renewing primary culture grown from dividing stem cells that self-organise similar to organogenesis in vivo. Organoids have demonstrated advantages over conventional in vitro models such as long-term genetic stability, tissue-specific architecture and maintaining the necessary cellular cross talk and behavioral characteristics of their primary corresponding cells. Organoids have been successfully gene edited to study cystic fibrosis and liver disease, and this may prove to be an invaluable resource to the ageing research field, especially with recent break-throughs in high-resolution lattice light-sheet microscopy allowing scientist to precisely observe the subcellular dynamics of living cells. In our lab with our collaborators at Liverpool Hospital we are growing organoids to study the molecular cell biology of liver injury and the progression of liver disease. We are also investigating the utility of organoids for precision medicine using patient derived tumour organoids for prospective drug screening.