Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of plastic-adherent cells that exhibit a fibroblast-like morphology, generate colony-forming units (CFU-Fs) and can differentiate into osteoblasts, adipocytes, and chondrocytes, among others.
In order to address the variability within MSC populations, the International Society for Cellular Therapy (ISCT) released a position paper stating the minimal criteria required for MSCs definition. Human MSCs are defined by positive expression of the cell surface antigens CD73, CD90, CD105 and by absence of expression of hematopoietic antigens, including CD11b or CD14, CD34, CD45, CD79 or CD19, and HLA-DR.
Mesenchymal stem cells can be expanded through multiple passages in medium containing high concentrations of fetal bovine serum (FBS); only a fraction of the cells will remain clonogenic through propagation. Due to changes in proliferation rates during expansion, it is advisable to not expand hMSCs beyond four or five passages.
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are obtained by isolating mononucleated cells from a marrow aspirate by centrifugation on a density gradient, followed by adherent cell expansion in tissue culture. MSCs are subsequently expanded by plating at a low density, which enhances the percentage of rapidly proliferating cells.
BM-MSCs demonstrate broad therapeutic potential, as seen by their angiogenesis-promoting capacities and their immunomodulatory properties. MSCs have been extensively tested in preclinical and clinical studies, and have led to promising results in treatment of numerous diseases.