Organoids in the Study of Aging

Over the course of the past twenty years, researchers have established the techniques needed to grow small volumes of functional tissue for many organ types. Lacking blood vessel networks, these organoids are at most a few millimeters in size; any larger and nutrients cannot perfuse to the innermost cells. There will be a use for organoids grown from a patient's own cells or from universal cell lines in transplantation therapies, such as those developed by Lygenesis. As researchers note here, however, by far the greatest use at present is to produce models for research.

Patient-derived organoids are self-organized 3D tissue cultures that are derived from stem cells. Isolated patients' stem cells differentiate to form an organ-like tissue comprising multiple cell types. Organoids have self-renewal and self-organization capabilities and retain the characteristics of the physiological structure and function of their source. Recent culturing advances aim to create the right environment for the stem cells so they can follow their own genetic instructions to self-organize, forming organoid structures that resemble miniature organs composed of many cell types. This approach provides tractable in vitro models of human physiology and pathology, thereby enabling interventional studies that are difficult or impossible to conduct in human subjects.

The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans, and cell cultures. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people.

Organoid culture technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging, and to design personalized approaches for the prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging, paving the way to personalized interventions targeting the biology of aging.

Link: https://doi.org/10.3390/ijms221910547

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