Objective: This article aims to explore the aging of mesenchymal stem cells (MSCs) during cell expansion and available methods to restore their quality. Materials and methods: we searched articles in PubMed/Medline and our library to collect relevant publications of MSC aging, their microenvironment (niche), and various approaches to prevent MSC aging. Results and Discussion: MSC expansion during culture may cause cell aging, which is reflected by change in growth, geno-type, and phenotype that can be seen in morphology and function. There are various approaches that can be used to prevent MSC aging. Approaches to prevent MSC aging in culture can be done by various methods, including by determining donor characteristics, genetic engineering approaches, regulating stem cells microenvironment in vitro, and in vitro physical modification Conclusion: Prevention of MSC aging during culture can be done by selection of MSC sources, genetic modification, and microenvironment and physical adjustments. ©2021 Japan University of Health Sciences & Japan International Cultural Exchange Foundation.