Identification of mesenchymal stem cells in perinodular fat and skin in XXXX : a potential source of myofibroblasts with implications for pathogenesis and therapy.

@entity18190 @entity5399 @entity5741 @entity12359 @entity74 @entity2074 @entity923 @entity2280 @entity436
@entity2074 ( @entity2074 ) is a @entity74 characterized by aberrant proliferation of myofibroblasts, the source of which remains unknown. Recent studies indicate that circulating and tissue-resident mesenchymal stem cells (MSCs) can differentiate into myofibroblasts. Therefore, the aim of this study was to profile MSCs from phenotypically distinct @entity2074 sites including cord, nodule, skin overlying nodule (SON), and perinodular fat (PNF) compared with unaffected internal controls, that is, distant palmar fat (DPF) and transverse palmar fascia (Skoog's fibers) as well as external control @entity923 ( @entity923 ) tissue including skin, fat, and fascia. Freshly isolated primary fibroblasts as well as cells grown up to passage 5 (P5) from @entity2074 (n=27) and @entity923 (n=14) samples were analyzed for the presence of established MSC markers @entity12359 , @entity5399 , and CD105 and absence of hematopoietic marker @entity2280 using fluorescence-activated cell sorting, in-cell quantitative western blotting, immunohistochemistry, and immunocytochemistry. Freshly isolated cells from SON, PNF, and cord biopsies had a higher number of @entity2280 (-)73(+)90(+)105(+) cells compared with Skoog's fibers and @entity923 controls. P3 cells obtained from all @entity2074 biopsies compared with @entity923 samples differentiated into osteocytes, adipocytes, and chondrocytes. P3 cord and nodule cells expressed intense a-smooth muscle actin staining compared with skin and fat cells. Stem cell markers including stem cell factor, MSC-homing marker @entity436 , and Wnt/b-catenin downregulator @entity5741 were all upregulated in SON and PNF compared with @entity923 skin and @entity923 fat, respectively, as shown by real-time quantitative polymerase chain reaction. However, osteogenic marker @entity18190 had a significantly higher expression in the PNF (P=0.002) and cord (P=0.01) compared with the nodule. In conclusion, we have shown the presence of MSCs in specific @entity2074 tissue phenotypes compared with internal and external control tissue. These findings provide preliminary support for a potential alternative source of disease myofibroblasts originating from sites such as SON and PNF as opposed to palmar fascia alone.
