Mesenchymal stem cells (MSCs) are the primary cell source in cell therapy and regenerative medicine due to its extraordinary self-renewing capacity and multilineage differentiation potential. Clinical trials involving MSCs are being conducted in a range of human diseases and the number of registered cases is continuously increasing. However, a wide gap exists between the number of MSCs obtainable from the donor site and the number required for implantation to damage tissues, and also between MSC scalability and MSC phenotype stability. The clinical translation of MSCs necessitates a scalable expansion bioprocess for the biomanufacturing of therapeutically qualified cells. This review presents current achievements for expansion of MSCs. Issues involving culture condition modification, bioreactor systems, as well as microcarrier and scaffold platforms for optimal MSC systems are discussed. Most importantly, the gap between current MSC expansion and clinical application, as well as outbreak directions for the future are discussed. The present systemic review will bring new insights into future large-scale MSC expansion and clinical application.
Keywords: MSC expansion; MSC proliferation and differentiation; bioreactors; clinical translation of MSCs; tissue engineering; xeno-free.