title: Differentiation of blood T cells: Reprogramming human induced pluripotent stem cells into neuronal cells.
abstract: BACKGROUND
  Human induced pluripotent stem cells (iPSCs) morphologically and functionally resemble human embryonic stem cells, which presents the opportunity to use patient-specific somatic cells for disease modeling and drug screening. In order to take one step closer to clinical applications, it is important to generate iPSCs through a less invasive approach and from any accessible tissue, including peripheral blood. Meanwhile, how to differentiate blood cell-derived iPSCs into neuron-like cells is still unclear.
  
  
  METHODS
  We utilized Epstein-Barr nuclear antigen-1-based episomal vectors, a nonviral system that can reprogram somatic cells into iPSCs in both feeder-dependent and feeder-free conditions, to generate iPSCs from T cells via electroporation and then induce them into neuronal cells.
  
  
  RESULTS
  We successfully isolated sufficient T cells from 20 mL peripheral blood of the donors and reprogrammed these T cells into iPSCs within 4 weeks. These iPSCs could be stably passaged to at least 50 passages, and exhibited the abilities of pluripotency and multiple-lineage differentiation. Notably, under the medium induction for 21 days, these T-cell-derived iPSCs could be differentiated into Nestin (neural progenitor marker)-, GFAP (glial cell marker)-, and MAP2 (neuron cell marker)-positive cells detected by immunofluorescence methods.
  
  
  CONCLUSIONS
  We have developed a safer method to generate integration-free and nonviral human iPSCs from adult somatic cells. This induction method will be useful for the derivation of human integration-free iPSCs and will also be applicable to the generation of iPSCs-derived neuronal cells for drug screening or therapeutics in the near future.
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC; Section of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Ping-Hsing
authors.initials: PH
authors.lastname: Tsai
authors.affiliation: Section of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Yun-Ching
authors.initials: YC
authors.lastname: Chang
authors.affiliation: National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Yi-Yen
authors.initials: YY
authors.lastname: Lee
authors.affiliation: Section of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Ko
authors.affiliation: Section of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Yang
authors.affiliation: National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Lin
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC; Section of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Yuh-Lih
authors.initials: YL
authors.lastname: Chang
authors.affiliation: National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Yu
authors.affiliation: National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Yang-Hsin
authors.initials: YH
authors.lastname: Shih
authors.affiliation: National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC; Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: mtchen@vghtpe.gov.tw.
authors.forename: Ming-Teh
authors.initials: MT
authors.lastname: Chen
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology*
keywords: Epstein-Barr nuclear antigen-1; T cells; electroporation; human-induced pluripotent stem cells; nonviral induced pluripotent stem cells