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

Abstract

Induced pluripotent stem cell-derived mesenchymal stem cell (iMSC) represent an important next step in regenerative medicine. By deriving mesenchymal stem cell-like cells from renewable induced pluripotent stem cell sources, researchers aim to overcome the donor variability, limited scalability, and senescence that have long constrained adult mesenchymal stem cell therapies. The recent study published in World Journal of Stem Cells by Ababneh et al illustrates how differences in derivation protocols can yield iMSC populations that are functionally and metabolically distinct despite meeting minimal mesenchymal stem cell criteria. This reinforces a key translational lesson: Protocol defines product. Moving forward, successful clinical translation will depend on aligning differentiation strategy with therapeutic purpose, integrating safety evaluation throughout development, and adopting manufacturing processes compatible with good manufacturing practice standards. Beyond marker expression, emphasis must now shift toward potency, standardisation, and indication-relevant critical quality attributes. Through such alignment, iMSC technologies may finally achieve reproducibility, safety, and therapeutic reliability.

Keywords: Induced pluripotent stem cell-derived mesenchymal stem cell; Induced pluripotent stem cell; Mesenchymal stem cell; Good manufacturing practices; Potency assay; Critical quality attribute; Clinical translation

Core Tip: This editorial highlights the emerging principle that in induced pluripotent stem cell-derived mesenchymal stem cell (iMSC) development, protocol defines product. Drawing on recent comparative data, it underscores how different derivation routes yield functionally distinct iMSCs despite meeting minimal mesenchymal stem cell criteria. The piece advocates aligning differentiation methods with therapeutic mechanisms, embedding genomic safety early, and designing good manufacturing practices-ready, comparable manufacturing processes. By integrating biological insight with process discipline, iMSC technology can achieve reproducibility, potency, and safety, thereby turning conceptual promise into clinically reliable cell therapies.