Enhancement of Replication and Differentiation Potential of Human Bone Marrow Stem Cells by Nicotinamide Treatment

Background and Objectives: Therapies using mesenchymal stem cells (MSCs) generally require substantial expansion of cell populations. However, the replicative life span of MSCs is limited and their multipotency declines over continued passages, imposing a limitation on their application especially in aged individuals. In an effort to increase MSC life span, we tested the effects of nicotinamide (NAM), a precursor of NAD(+), that has been shown to reduce reactive oxygen species generation and delay the onset of replicative senescence in fibroblasts. Methods: Bone marrow stem cells (BMSCs) from healthy donors were cultivated in the presence of 5 mM NAM until the end of their life span. The levels of proliferation and differentiation to osteogenic, adipogenic, and chondrogenic lineages of BMSCs were compared between populations incubated in the absence or presence of NAM. Results: The replicative life span was substantially increased with a significant delay in the onset of senescence, and differentiation to all tested lineages was increased. Furthermore, differentiation was sustained and the adipogenic switch from osteogenesis to adipogenesis was attenuated in late-passage BMSCs. Conclusions: NAM could be considered as an important biological agent to expand and sustain the multipotency of BMSCs and thus broaden the application of stem cells in cell therapies.