Pluripotent stem cells as a source of osteoblasts for bone tissue regeneration.

Appropriate and abundant sources of bone-forming osteoblasts are essential for bone tissue engineering. Pluripotent stem cells can self-renew and thereby offer a potentially unlimited supply of osteoblasts, a significant advantage over other cell sources. We generated mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) from transgenic mice expressing rat 2.3 kb type I collagen promoter-driven green fluorescent protein (Col2.3GFP), a reporter of the osteoblast lineage. We demonstrated that Col2.3GFP ESCs and iPSCs can be successfully differentiated to osteoblast lineage cells that express Col2.3GFP in vitro. We harvested GFP+ osteoblasts differentiated from ESCs. Genome wide gene expression profiles validated that ESC- and iPSC-derived osteoblasts resemble calvarial osteoblasts, and that Col2.3GFP expression serves as a marker for mature osteoblasts. Our results confirm the cell identity of ESC- and iPSC-derived osteoblasts and highlight the potential of pluripotent stem cells as a source of osteoblasts for regenerative medicine.