Protocol defines product: Navigating function, safety and translation of induced pluripotent stem cell-derived mesenchymal stem cells

Table 1 Evolving focus in the evaluation of mesenchymal stem cell products

Evaluation focus	Traditional MSC approach	Next-generation iMSC perspective
Cell identity	ISCT minimal criteria (CD73/CD90/CD105, tri-lineage differentiation)	ISCT + transcriptomic, metabolic, and functional profiling
Potency	Generic immunosuppression or differentiation assays	Indication-specific assays aligned with mechanism of action
Safety	Karyotype, sterility, mycoplasma (often late-stage)	Integrated genomic surveillance, residual pluripotency and tumorigenicity testing from early development
Manufacturing	Often donor-dependent, Matrigel or foetal bovine serum	Xeno-free, chemically defined, good manufacturing practices-compatible and comparable
Reproducibility	Limited by donor and passage variability	Enabled through renewable induced pluripotent stem cells source + defined process control

While traditional mesenchymal stem cell assessments emphasised minimal phenotypic criteria, induced pluripotent stem cell-derived mesenchymal stem cell development increasingly requires function- and safety-based qualification. MSC: Mesenchymal stem cell; iMSC: Induced pluripotent stem cell-derived mesenchymal stem cell; ISCT: International Society for Cell & Gene Therapy.