UC San Diego

Mesenchymal stem cells (MSCs) have great potential in tissue engineering as they can be easily isolated, differentiated into several lineages (cartilage, bone, fat), and allogeneically transplanted without immune response. For developing therapies to be clinically translated, it is imperative to understand how donor characteristics, such as age, affect the efficacy of MSC- based treatments. The overall aim of this study was to characterize age-related changes in MSCs from bone marrow using a murine model. First, the conditions for isolation and in vitro expansion were optimized for bone marrow- derived MSCs; MSCs were isolated from C57Bl/6 mice of varying age (three-week, two-month, six-month, ten-month, and thirteen-month old). Second, donor age-dependent changes in expansion ability were determined by investigating the population doubling time and colony- forming capability of MSCs from various age groups. Cell populations from older mice proliferated more quickly and produced more colonies than their younger counterparts. Finally, age-related changes in MSC functionality and differentiation potential were investigated. Migration rate, antioxidant levels, and cytoskeletal dynamics of each population were determined. It was found that the older populations had faster migration and more dynamic cytoskeletons, while the younger cells had higher antioxidant activity. The cells were also subjected to chondrogenic, osteogenic, and adipogenic assays. The intermediate-aged cells consistently underwent more adipogenesis, while osteogenesis increased until a peak age then declined, and chondrogenesis was not affected by age