Local fistula microenvironment

The local fistula microenvironment is a complex pathological niche characterized by chronic inflammation, tissue remodeling, and failed wound healing, most notably in perianal fistulizing Crohn's disease (Scharl et al., 2017, Journal of Crohn's and Colitis). This environment involves a synergistic interplay between immune cells, such as macrophages and T cells, myofibroblasts, and epithelial cells undergoing epithelial-to-mesenchymal transition (EMT) (Zimmerman et al., 2015, Gastroenterology). High levels of pro-inflammatory cytokines, particularly TNF-alpha and TGF-beta, drive the persistence of the fistulous tract and inhibit normal closure. The extracellular matrix within this microenvironment is often degraded by matrix metalloproteinases, further preventing structural integrity. Therapeutic strategies targeting this microenvironment aim to suppress the localized immune response and promote a pro-healing state. This is often achieved through systemic biologics like TNF inhibitors or local cell-based therapies such as mesenchymal stem cells, like darvadstrocel (Panés et al., 2016, The Lancet). These treatments work by modulating the cytokine profile and inducing regulatory T cell activity within the tract. Understanding the specific cellular and molecular components of this microenvironment is essential for improving the low rates of long-term fistula closure.

Other names

Fistulous tract microenvironmentPerianal fistula nicheCrohn's fistula microenvironment

Therapeutic intervention involves the modulation of the inflammatory milieu through cytokine inhibition or the introduction of mesenchymal stem cells to promote immunomodulation and tissue repair.