Bone marrow stromal cells act as feeder cells for tendon fibroblasts through soluble factors

Feeder effects of bone marrow stromal cells (BMSCs) on tendon fibroblasts were investigated using a co-culture method for the application of ligament or tendon tissue engineering and cell therapy. BMSCs had significant effects on enhancing cell proliferation, the ability of cells to migrate, and cell adhesivity but little effect on the extracellular matrix (ECM) synthesis of tendon fibroblasts without cell-cell contact. Furthermore, the conditioned medium from BMSCs, despite the existence of fibroblasts, significantly increased the number of fibroblasts. Based on these results, the mechanism of the feeder effects is considered to be a certain signal of soluble factors from BMSCs to the fibroblasts. Comparative proteome analysis of the conditioned medium from co-culture of fibroblasts and BMSCs revealed less expression of plasminogen, which showed inhibitory effects on fibroblast proliferation. With regard to the relationships between plasminogen and BMSCs in the co-culture system, we speculate that BMSCs allow resolution of plasminogen or its cleavage activity in the medium via some mechanism.