Tissue engineering to better understand senescence: Organotypics come of age

Abstract

The recent advent of ‘organs in a dish’ has revolutionised the research landscape. These 3D culture systems have paved the way for translational, post genomics research by enabling scientists to model diseases in the laboratory, grow patient-derived organoids, and unite this technology with other cutting-edge methodologies such as drug discovery. Fields such as dermatology and neuroscience have revolutionised the development of robust 3D models, which faithfully recapitulate native physiology in vivo to provide important functional and mechanistic insights. These models have underpinned a rapid growth in the number of organs and myriad of human diseases that can be modelled in 3D, which currently includes breast, cerebral cortex, heart, intestine, kidney, liver, lung, neural tube, pancreas, prostate, skin and stomach, as well as patient derived tumours. However, so far, they have not yet been employed extensively in the study of fundamental cellular programmes such as senescence. Thus, tissue engineering and 3D culture offer an exciting opportunity to further understand the bright and dark sides of senescence in a more complex and physiologically relevant environment. Below, we will discuss previous approaches to investigating senescence and ageing using organotypic models, and some potential opportunities for future research.

3D bioprinting—a model for skin aging

“…Other researchers have explored senescence in 3D human cartilage [ 78 ] and 3D and 2D cultured adipose-derived mesenchymal stem cells [ 79 ]. Other 3D models for cellular senescence are highlighted in Milligan et al [ 80 ] reviews.…”

Adult kidney explants is a physiologic model for studying diabetic nephropathy

“…One reason for the success of organotypic models is that these 3D assays have a number of advantages over traditional 2D assays [10,11], suggesting that native cellular behaviour could be better understood using 3D assays. Other systems, such as microchips, spheroids, hollow fibre bioreactors, bioprinting and the microfluidic integration of different tissue models, have reproduced systemic drug effects [12].…”