Frontiers in Medicine · Oct 14, 2026

Sinus tarsi adipose tissue as a neuro-adipose niche in progressive collapsing foot deformity: neural innervation and stem cell properties

By Mazzotti A, Arceri A, de Cesar Netto C et al.

PURPOSE: The adipose tissue of the sinus tarsi has traditionally been viewed as a passive structure. Emerging evidence indicates it may function as a biologically active, innervated microenvironment contributing to proprioception and tissue homeostasis. As a rich source of mesenchymal stem cells, it also holds regenerative potential. However, its neural characteristics and stem cell properties remain underexplored. METHODS: Adipose tissue samples were obtained from 20 patients undergoing surgery for symptomatic flatfoot deformity (progressive collapsing foot deformity - PCFD) and stratified by age (<18 vs. ≥ 18 years) and sex. Histology (H&E) and immunohistochemistry (S100, p75, PGP9.5) assessed neural elements, with quantitative analysis of immunopositive areas. Adipose-derived stem cells (ADSCs) were isolated and evaluated for viability (Alamar Blue) and osteogenic differentiation (gene expression: RUNX2, ALPL, COL1A1, BGLAP). RESULTS: Histology revealed preserved architecture with age-related stromal expansion, more pronounced in males ≥18 years. Neural markers are localized primarily to the stromal/vascular compartment, with p75 predominant across groups (p < 0.0001). Younger females showed highest neural marker expression; significant age-associated decline in patients with PCFD occurred in S100 and p75. ADSCs from younger females exhibited superior viability and early osteogenic marker expression, while aging correlated with reduced proliferation and a shift toward mature osteogenic phenotype, especially in males. CONCLUSION: The sinus tarsi harbors a dynamic neuro-adipose niche with age- and sex-dependent neural and stem cell features. This tissue may link proprioception with regenerative capacity and represents a promising autologous cell source for foot and ankle applications.

doi.org/10.3389/fmed.2026.1925286 Open access PubMed 42952849 Mechanisms