Molecular and Microenvironmental Regulation of Mesenchymal Stromal Cells and Their Secretome in Regeneration and Inflammation

Mesenchymal stromal cells (MSCs) represent a pivotal area of research in regenerative medicine, renowned for their ability to modulate immune responses, promote tissue repair, and maintain homeostasis. While the foundational understanding of MSC biology has evolved, persistent gaps remain in delineating the precise mechanisms by which these cells exert their multifaceted effects. Recent studies underscore the remarkable context-dependency of MSC function, highlighting the influence of both cell-intrinsic molecular pathways and a myriad of external microenvironmental cues. Modern investigations have also expanded the focus from MSCs themselves to the critical role of their secretome—a dynamically regulated array of soluble molecules, extracellular vesicles, bioactive lipids, metabolites, and matrix-remodeling factors that orchestrate cellular communication during repair and inflammation. Despite impressive advances, the heterogeneity in MSC function, secretome composition, and therapeutic efficacy presents ongoing challenges to reproducibility and clinical translation.This Research Topic aims to elucidate the molecular and environmental determinants that govern MSC identity, plasticity, and paracrine activity, fostering a more integrated and mechanistic understanding of their functional diversity. Central questions include how transcriptional, epigenetic, metabolic, and cell signaling networks interact with extrinsic factors—such as hypoxia, inflammatory mediators, extracellular matrix modifications, mechanical inputs, aging, and disease state—to define MSC fate and secretome composition. Investigations exploring extracellular vesicle biogenesis and cargo selection, the identification of potency markers, and the engineering or preconditioning approaches to modulate MSC function are especially encouraged. By bridging fundamental cellular mechanisms with translational objectives, this Research Topic seeks to clarify the drivers of MSC heterogeneity and accelerate the rational development of more targeted and effective regenerative and anti-inflammatory therapies.The scope of this Research Topic encompasses mechanistic, systems-level, and translational studies, but excludes unrelated cell types and non-therapeutic approaches. We welcome articles addressing, but not limited to, the following themes:- Molecular networks (transcriptional, epigenetic, metabolic, and signaling) dictating MSC identity and function- The impact of microenvironmental factors on MSC plasticity and secretome composition- Mechanisms of extracellular vesicle biogenesis, cargo loading, and paracrine signaling- Single-cell and systems-level analyses of MSC heterogeneity and potency markers- Strategies for preconditioning, engineering, or priming MSCs to enhance therapeutic reproducibility and efficacy- Clinical perspectives and models translating basic knowledge of MSCs and their secretome into regenerative or anti-inflammatory therapies Topic editors: Daiva Bironaite, Mohammad Mehedi Hasan, Rokas Miksiunas Source: https://www.frontiersin.org/research-topics/83601/molecular-and-microenvironmental-regulation-of-mesenchymal-stromal-cells-and-their-secretome-in-regeneration-and-inflammation