Peripheral nerve-derived adult pluripotent stem (NEDAPS) cells for induction to osteoblast as a cell therapy in segmental bone defect fractures

Abstract

The segmental defect fractures in bone can result from various types of causes such as primary injury, fracture, developmental deformities, after the debridement of bone in osteomyelitis, or resection of bone tumor. These segmental bone defect fractures impose various problems such as clinical and socioeconomic that would negatively affect a patients’ quality of life. These patients often undergo repeated surgical procedures to treat segmental bone defects and their hospital stays are often significantly prolonged. In our research, we have been characterizing a newly identified population of peripheral nerve-derived pluripotent stem cells (NEDAPS) and evaluating the differentiating potential of these cells to osteoblasts, which we are postulating to use to repair segmental bone defect fractures in a mouse model. Our hypothesis is that the natural functions of the NEDAPS cells in peripheral nerve tissue are to detect or report tissue injury in order to supply pluripotent stem cells locally, which are induced to certain functional cells (osteoblasts) to produce tissue such as bone in segmental bone defect cases. These induced osteoblasts showed the following properties, which suggest that NEDAPS cells can be induced to osteoblasts: 1) In vitro results revealed the changes in the morphological appearance of NEDAPS cells to that of osteoblasts in the presence of osteoblast-induction medium and 2) Induced osteoblasts are positive for alkaline phosphatase and type I collagen stains. Furthermore, RT-PCR assay showed that the induced osteoblasts expressed the genes that are normally expressed by osteoblasts at different stages of maturation. Animal study indicated that the fluorescent cell membrane-labeled NEDAPS and osteoblastic cells were viable at fracture sites. Immunofluorescence staining of osteocalcin and collagen I in induced osteoblasts at fracture sites showed cell growth and participation in bone healing process. This study suggests that NEDAPS induced osteoblasts can be a potential source in the treatment of segmental bone defect fractures.