Mesenchymal stem cells are an easily obtainable stem cell source from bone marrow. Presently, they are the most widely used cell type for cellular replacement strategies in humans as a result of extensive research that has demonstrated that these cells are capable of self-renewal, able to undergo multi-lineage differentiation, engraft, and ameliorate symptoms in numerous animal models. In this study, we comprehensively characterize human second trimester mesenchymal stem cells (STMSCs). We demonstrate that STMSCs are easily expandable to clinical relevance and express pluripotent markers such as Oct-4, Nanog, Sox-2, and SSEA-4 at the cellular and molecular level. Moreover, we directionally differentiate STMSCs into osteogenic, chondrogenic, adipogenic, neurogenic, and cardiogenic cell lineages. These studies demonstrate the plasticity of STMSCs and the potential for their use in cellular replacement therapy. (c) 2007 Elsevier Inc. All rights reserved.