microenvironmentfibroblasts

Microenvironment fibroblasts are resident stromal cells found within tissue microenvironments that regulate extracellular matrix composition, intercellular signaling, and tissue mechanics. They derive from mesenchymal lineages and are distributed across most organs. In normal conditions they maintain ECM turnover, produce basement membrane components, and respond to cues from epithelial, immune, and endothelial cells to preserve tissue architecture and function.

These fibroblasts are highly heterogeneous, varying by tissue type and physiological state. They can be identified by a combination of markers, such as vimentin and PDGFR-α, and by functional profiles, since no single universal marker exists. When tissue is injured or stressed, microenvironment fibroblasts can become activated and differentiate into myofibroblasts, which exhibit enhanced contractility and increased synthesis of ECM components like collagen I and fibronectin. This activation supports wound healing and scar formation but can contribute to pathological fibrosis if unresolved.

In health, microenvironment fibroblasts participate in development, maintenance of tissue integrity, and resolution of inflammation. In disease, they play a central role in fibrotic disorders (such as hepatic or pulmonary fibrosis) and shape the tumor microenvironment in cancer. In tumors, fibroblasts—often referred to as cancer-associated fibroblasts—modulate ECM remodeling, secrete growth factors, and influence immune cell infiltration, with effects that can be either pro-tumorigenic or sometimes restraining tumor growth depending on context.

Ongoing research uses single-cell and spatial transcriptomics to map fibroblast subtypes and their interactions within specific microenvironments. Therapeutic efforts aim to modulate fibroblast activation and ECM remodeling, but faces challenges due to functional heterogeneity and essential roles in normal tissue homeostasis.