When Viability Persists but Futures Collapse: Structural Limits of Mesenchymal Stromal Cell–Based Regenerative Strategies

Mesenchymal stromal cell (MSC)–based therapies are commonly evaluated through metrics of survival, differentiation, and short-term functional outcomes. Yet a growing body of experimental evidence shows a recurring paradox: MSC constructs may remain viable, integrated, and locally functional while failing to sustain long-term regenerative trajectories. In this Perspective, we argue that this paradox cannot be resolved at the level of cellular performance alone. We introduce a structural distinction between local biological viability and global accessibility of regenerative futures. Building on recent work in regenerative medicine and on a formal framework of irreversible accessibility developed by the author, we show that many MSC strategies may cross irreversible structural thresholds at which future regenerative options are silently lost, despite preserved viability. This perspective reframes negative or ambiguous results not as experimental failure, but as manifestations of an unrecognised loss of biological accessibility. The implications concern experimental design, interpretation of in vivo success, and the limits of post-hoc optimisation.