Exploring Microenvironment Strategies to Delay Mesenchymal Stem Cell Senescence

Mesenchymal stem cells (MSCs) have recently emerged as an important candidate for cell therapy and tissue regeneration. However, some limitations in translational research and therapies still exist, such as insufficient cell supply, inadequate differentiation potential, and decreased immune capacity, all of which result from replicative senescence during long-term in vitro culture. In vitro, stem cells lack a protective microenvironment owing to the absence of physical and biochemical cues compared with the in vivo niche, which provides dynamic physicochemical and biological cues. This difference results in accelerated aging after long-term in vitro culture. Therefore, it remains a great challenge to delay replicative senescence in culture. Constructing a microenvironment to delay replicative senescence of MSCs by maintaining their phenotypes, properties, and functions is a feasible strategy to solve this problem, and has made measurable progress both in preclinical studies and in clinical trials. Here, we review the current knowledge on the characteristics of senescent MSCs, explore the molecular mechanisms of MSCs senescence, describe the niche of MSCs, and discuss some current microenvironment strategies to delay MSCs replicative senescence that can broaden their range of therapeutic applications.