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Induction of dental pulp-derived induced pluripotent stem cells in the absence of c-Myc for differentiation into neuron-like cells
Institution:1. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC;2. National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC;3. School of Dentistry, National Yang-Ming University, Taipei, Taiwan, ROC;4. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC;5. Division of Oral and Maxillofacial Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC;6. Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC;7. Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
Abstract:BackgroundA recent research breakthrough has demonstrated that the ectopic expression of four genes is sufficient to reprogram human fibroblasts into inducible pluripotent stem cells (iPSCs). However, whether human dental pulp cells (DPCs) could be reprogrammed into iPSCs remains an open question. In this study, we demonstrated that DPCs from deciduous and permanent teeth can be reprogrammed into iPSCs without c-Myc and had the capacity to differentiate into neuron-like cells.MethodsDPCs were obtained from donors and reprogrammed into iPSCs using retroviral transduction with SOX2, OCT4, and KLF4. Then, these iPSCs were differentiated into neuron-like cells. Microarray and bioinformatics were used to compare the gene expression profile among these iPSCs and iPSC-derived neuron-like cells.ResultsThe DPCs displayed a high vitality and capability to quickly restart proliferation and expressed elevated pluripotency similar to mesenchymal stem cells. According to our results, DPC-derived iPSC colonies that could be subcultured and propagated were established as early as 10 days after transduction, in comparison with the skin fibroblast (DPC-derived iPSCs) without c-Myc presented embryonic stem cell-like properties and the pluripotent potential to differentiate into neuron-like cells, which resemble neurons both morphologically and functionally.ConclusionThe human DPCs from deciduous and permanent teeth can undergo reprogramming to establish pluripotent stem cell lines without c-Myc. These surgical residues, usually regarded as medical waste, can be used as an alternative source of pluripotent stem cells for personalized medicine.
Keywords:dental pulp  differentiation  inducible pluripotent stem cells  neural cell
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