The Need to Update Quality Control Standards in Good Manufacturing Practices for Mesenchymal Stem Cells: Inclusion of Apoptosis and Senescence Assessment

Mesenchymal stem/stromal cells (MSCs) are gaining increasing attention for potential clinical ap- plications due to their regenerative and immunomodulatory properties. However, quality control checks under contemporary good manufacturing practices, which typically adhere to the minimal criteria proposed by the International Society for Cellular Therapy, are insufficient because they assess MSC identity rather than functional competency. Accumulating evidence indicates that apoptosis and senescence significantly impact MSC potency, viability, and immunomodulation potential following infusion. Notably, apoptotic or senescent MSCs can alter secretome profiles, disrupt therapeutic efficacy, and pose safety concerns. Herein, we propose adding apoptosis and senescence assessments to the standard quality control checks for MSCs by incorporating meth- ods such as annexin A5 (ANXA5/annexin V) and propidium iodide staining, caspase activity assess- ment, senescence-associated b -galactosidase staining, and quantification of senescence-related gene expression (cyclin-dependent kinase inhibitors 1A (CDKN1A/p21) and 2A (CDKN2A/p16), and tumor protein p53 [TP53]). Such changes will enable the incorporation of functional markers and enhance the consistency, predictability, and clinical utility of MSC-based products. Harmonizing quality control strategies with new biological knowledge is crucial for creating next-generation cell therapeutics.