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

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.

• mesenchymal stem cells
• retropatellar fat-pad
• peripheral blood mononuclear cells
• ACL fibroblasts
• co-cultureand

Acknowledgments

We thank Dr. Ronald Mathieu (Division of Hematology/Oncology Flow Cytometry Core, Children’s Hospital Boston, Boston, MA) for FACS support, and Dr. Patrick Vavken, Dr. Arthur Nedder, Kathryn Mullen, and Dana Bolgen (all ARCH, Children’s Hospital Boston) for help with tissue collection.

Declaration of interest

The authors declare that they have no financial, consulting, and personal relationships with other people or organizations that could influence the author’s work. This work was supported by the NIH/NIAMS grant number R01AR054099.