Abstract
Adult stem cells are a promising cell source for cartilage regeneration. Unfortunately, due to donor age and ex vivo expansion, stem cell senescence becomes a huge hurdle for these cells to be used clinically. Increasing evidence indicates that environmental preconditioning is a powerful approach in promoting stem cells' ability to resist a harsh environment post-engraftment, such as hypoxia and inflammation. However, few reports organize and evaluate the literature regarding the rejuvenation effect of environmental preconditioning on stem cell proliferation and chondrogenic differentiation capacity, which are important variables for stem cell based tissue regeneration. This report aims to identify several critical environmental factors such as oxygen concentration, growth factors, and extracellular matrix and to discuss their preconditioning influence on stem cells' rejuvenation including proliferation and chondrogenic potential as well as underlying molecular mechanisms. We believe that environmental preconditioning based rejuvenation is a simpler and safer strategy to program pre-engraftment stem cells for better survival and enhanced proliferation and differentiation capacity without the undesired effects of some treatments, such as genetic manipulation.