Functionally compromised synovium-derived mesenchymal stem cells in Charcot neuroarthropathy

Charcot neuroarthropathy (CNA) often presents as a diabetic foot complication. The role of synovial mesenchymal stem cells (syn-MSCs) in the pathogenesis of CNA is unclear. Synovial samples were collected, for isolation of syn-MSCs, from diabetic patients with CNA (n = 7) and non-diabetic patients with intra-articular fracture or normal joints (non-CNA; n = 7) during foot surgery. The syn-MSCs in the CNA and non-CNA groups were characterized comparatively. The average number of colonies formed in the CNA group was 6 ± 3.5 per half plate (10 mm in diameter), while it was 43 ± 21.6 in the non-CNA group (p < 0.05). The average size (pixels) of the colonies in the CNA group was smaller than that in the non-CNA group. When the colonies were stratified into high-, medium- and low-density subgroups, colonies in the high-density subgroup of the CNA group were reduced in density. Expression of PPAR-γ, RUNX2, Sox9 and type II collagen by syn-MSCs in the CNA group was decreased during adipogenic, osteogenic and chondrogenic differentiation as compared with the non-CNA group. In conclusion, syn-MSCs in CNA joints were reduced in number, with declined differentiation potentials. The high-density subpopulation of the syn-MSCs was particularly affected by the pathology of CNA.