Human primary fibroblasts perform similarly to MSCs in assays used to evaluate MSC safety and potency

BACKGROUND: Cellular therapeutic agents may benefit trauma patients by modulating the immune response to injury, and by reducing inflammation and vascular leakage. Administration of allogeneic mesenchymal stromal cells (MSCs) shows some benefit in preclinical and clinical trials, but less testing has been performed with other cell types. Human primary fibroblasts (FBs) were compared to MSCs in assays designed to evaluate MSCs to determine if these assays actually evaluate properties unique to MSCs or whether related cell types perform similarly. STUDY DESIGN AND METHODS: MSC-related surface marker expression, tissue factor, and human leukocyte antigen–D related were evaluated by flow cytometry, and in vitro adipogenic and osteogenic differentiation potential were determined. Procoagulant activity was determined by thromboelastography. Two potency assays correlated with immunomodulation potential were utilized: the mixed lymphocyte reaction and indoleamine 2,3-dioxygenase enzyme activity assays. RESULTS: Human primary FBs performed similarly to MSCs in assays designed to evaluate MSC characteristics and potency. Although similar for MSC-positive cell surface marker expression, FBs did not show robust adipose differentiation and expressed some level of markers not expected on MSCs. CONCLUSIONS: Human primary FBs are very similar to human MSCs, at least in assays currently used to evaluate MSC potency. Preclinical and clinical testing are required to determine if FBs show similar activity to MSCs in vivo. If FBs show inferior activity in vivo, development of new MSC-specific potency assays will be necessary to evaluate properties relevant to their unique clinical benefits.