title: Blood cell-derived induced pluripotent stem cells free of reprogramming factors generated by Sendai viral vectors.
abstract: The discovery of induced pluripotent stem cells (iPSCs) holds great promise for regenerative medicine since it is possible to produce patient-specific pluripotent stem cells from affected individuals for potential autologous treatment. Using nonintegrating cytoplasmic Sendai viral vectors, we generated iPSCs efficiently from adult mobilized CD34⁺ and peripheral blood mononuclear cells. After 5-8 passages, the Sendai viral genome could not be detected by real-time quantitative reverse transcription-polymerase chain reaction. Using the spin embryoid body method, we showed that these blood cell-derived iPSCs could efficiently be differentiated into hematopoietic stem and progenitor cells without the need of coculture with either mouse or human stromal cells. We obtained up to 40% CD34⁺ of which ~25% were CD34⁺/CD43⁺ hematopoietic precursors that could readily be differentiated into mature blood cells. Our study demonstrated a reproducible protocol for reprogramming blood cells into transgene-free iPSCs by the Sendai viral vector method. Maintenance of the genomic integrity of iPSCs without integration of exogenous DNA should allow the development of therapeutic-grade stem cells for regenerative medicine.
authors.affiliation: Department of Medicine and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA. lin.ye@ucsf.edu
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Muench
authors.forename: Noemi
authors.initials: N
authors.lastname: Fusaki
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Beyer
authors.forename: Jiaming
authors.initials: J
authors.lastname: Wang
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Qi
authors.forename: Jingwei
authors.initials: J
authors.lastname: Yu
authors.forename: Yuet Wai
authors.initials: YW
authors.lastname: Kan
mesh_terms: D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005822:Genetic Vectors / Q000378:metabolism*; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D029082:Sendai virus / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D014157:Transcription Factors
keywords: CD34+; Differentiation; Hematopoietic progenitors; Reprogramming