Transdifferentiation Potential of Human Bone Marrow Derivedmesenchymal Stem Cells

INTRODUCTION Transdifferentiation is a process that one cell type of a developmental lineage switches into another cell type of a different lineage through genetic reprogramming. Even though this process has been well studied and established in amphibian systems, it is unclear if mammalian cells possess the same potential, since it is generally thought that mammalian cells lose their differentiation capacity once they commit to a particular developmental lineage. Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells, present in many adult tissues, including bone marrow, trabecular bone, fat, and muscle. In response to specific culture conditions, these cells can give rise to multiple mesenchyme derived cell types, such as osteoblasts, chondrocytes, adipocytes, and myoblasts. Additionally, in vivo transplantation studies in rodents have shown that MSCs can replenish the whole bone marrow system and generate not only mesodermal cells, but also cells characteristic of neuroectodermal and endodermal lineages, suggesting that transdifferentiation occurs in mammalian system. However, the regulation of lineage commitment in adult human MSCs is poorly understood; in particular, it is unclear if hMSCs that are pre-committed to one cell type maintain their multidifferentiation potential. In this study, we developed an in vitro differentiation strategy, coupled with lineage-specific cell sorting, to assess if hMSCs that have differentiated into a given mesenchymal cell lineage can transdifferentiate into other cell types in response to inductive extracellular cues. METHODS Isolation and Expansion of hMSCs hMSCs were isolated from bone marrow aspirate obtained during total hip arthroplasty with institutional IRB approval, and cultured in basal medium containing DMEM, 10% FBS, and antibiotics.