Mesenchymal stem/stromal cells and regenerative medicine.

Abstract

Mesenchymal stem/stromal cells (MSCs) continue to drive innovation in regenerative medicine, yet the field is undergoing a critical evolution from the early concept of cellular engraftment to complex paracrine-mediated tissue repair. This review systematically evaluates the core scientific questions defining this transition, highlighting the latest advancements in MSC biology and the rapidly expanding therapeutic frontier of MSC-derived extracellular vesicles (MSC-EVs). We critically appraise recent progress in decoding MSC therapeutic mechanisms, specifically their profound capacity for immune modulation and microenvironmental remodeling. By synthesizing current findings across diverse and challenging clinical applications-encompassing oral tissue regeneration, osteoarthritis, and complex immune disorders-we provide expert insights into the discrepancies between promising preclinical data and variable clinical outcomes. Crucially, we address persistent translational bottlenecks, including inherent donor heterogeneity, manufacturing scalability, and the lack of standardized potency assays. It is our perspective that overcoming these limitations demands a strategic pivot towards precise cell-free MSC-EV therapies and advanced bioengineering strategies. Ultimately, this review highlights key directions for future research. By connecting basic mechanistic insights with clinical demands, we aim to accelerate the translation of effective MSC-based therapies.