Pim-1 Kinase Cooperates with Serum Signals Supporting Mesenchymal Stem Cell Propagation

Mesenchymal stem cells (MSCs) are currently undergoing testing in several clinical settings. The propagation of MSCs from multiple species in culture is an important step in furthering our understanding of these progenitor cells. Pim-1, a proto-oncogenic serine/threonine kinase, regulates cell proliferation, survival, and differentiation. Although it has been shown that Pim-1 participates in signal transduction mediating mitogenic action in MSCs, its roles in the modulation of MSC propagation remain to be defined. Understanding of ovine MSCs transduced with Pim-1 may provide improved ovine models for cellular therapy development. Using genetically modified ovine MSCs that constitutively overexpressed Pim-1 (MSC expressing PIM-1 and ZsGreen protein), we evaluated the impact of elevated Pim-1 activity on the proliferation, survival, and differentiation of MSCs in culture. Our results showed that Pim-1 enhanced the intrinsic molecular signals of growth and survival implicated in the mediation of serum signaling under normal culture conditions (10% serum). We found that Pim-1 promoted MSC proliferation irrespectively of the serum concentration, but with a decreased proliferation rate compared to increased serum concentrations, relative to the control vector-transduced MSC expressing ZsGreen protein. Further, Pim-1 prevented MSC apoptosis induced by hypoxia or serum deprivation as evidenced by enhanced mitochondria integrity and reduced annexin V binding. Interestingly, the phenotype and multilineage differentiation potential of the cells were not influenced by Pim-1. Taken together, these observations demonstrate that Pim-1 kinase cooperates with exogenous serum signals supporting MSC propagation in the ovine model.