Mesenchymal Stem Cells from the Retropatellar Fat Pad and Peripheral Blood Stimulate ACL Fibroblast Migration, Proliferation, and Collagen Gene Expression

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Abstract
Mesenchymal stem cells (MSCs) have been of recent interest as adjuncts for ligament repair. However, the effect of these cells on the resident ligament fibroblasts has not yet been defined. In this study, we hypothesized that co-culture of MSCs and ligament fibroblasts would result in increases in the proliferative rate of the ligament fibroblasts and their expression of collagen-related genes, as well as differentiation of the MSCs down a fibroblastic pathway. In addition, we hypothesized that these effects would be dependent on the source of the MSCs. Porcine MSCs were isolated from both the retro-patellar fat pad (ADSCs) and the peripheral blood (PBMCs) and co-cultured with porcine anterior cruciate ligament (ACL) fibroblasts. Fibroblast migration, proliferation, and collagen gene expression were evaluated at time points up to 14 days. ADSCs had a greater effect on stimulating ACL-fibroblast proliferation and procollagen production, while PBMCs were more effective in stimulating ligament fibroblast migration. In addition, co-culture with the ACL fibroblasts led to significant increases in collagen gene expression for ADSCs, suggesting a differentiation of these cells down a fibroblastic pathway during the co-culture period. This was not seen for the PBMCs. Thus, the effects of MSCs on in situ ACL fibroblasts were found to be source dependent, and the choice of MSC source should take into account the different performance characteristic of each type of MSC.

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