Growth,Metabolism,and Growth Inhibitors of Mesenchymal Stem Cells

Abstract

Most therapeutic applications of bone marrow stromal cells (MSCs), or mesenchymal stem cells, require expansion of these cells. This study aimed to obtain more information about human MSCs regarding their expansion characteristics: growth, metabolism, and growth inhibitors. In addition, the same expansion factors were examined for (model species) goat and rat MSCs to evaluate differences between MSCs of mammalian species. MSC proliferation, nutrient consumption, and metabolite production were determined for five donors per species. In addition, the growth inhibitory concentrations of lactate and ammonia (NH₃) were established. Results showed that goat MSCs grew significantly faster than human and rat MSCs and that goat cells metabolized glucose more efficiently into energy (Y_lac/glc = 0.8) than human (Y_lac/glc = 2.0) and rat MSCs (Y_lac/glc = 1.9). In addition, human (qGlc = −9.2 pmol cell⁻¹ day⁻¹) and rat MSCs (qGlc = −5.9 pmol cell⁻¹ day⁻¹) consumed more glucose than goat MSCs (qGlc = −2.6 pmol cell⁻¹ day⁻¹). Glutamine was shown not to be important as energy source for human, goat, and rat MSCs. Regarding growth inhibition by metabolites, rat MSCs were more sensitive to lactate and NH₃ (growth inhibiting at 16 mM lactate and at 1.9 mM NH₃) than goat (lactate: 28.4 mM, NH₃: 2.9 mM) and human MSCs (lactate: 35.4 mM, NH₃: 2.4 mM). Human MSCs did not lose their differentiation potential when their growth was inhibited by lactate or NH₃.