NDLI: Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells.

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Adenoviral gene delivery can reprogram human fibroblasts to induced pluripotent stem cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhou, Wenbo Freed, Curt R.
Description	Country affiliation: United States Author Affiliation: Zhou W ( Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado 80045, USA. wenbo.zhou@ucdenver.edu)
Abstract	Mouse and human fibroblasts have been transformed into induced pluripotent stem (iPS) cells by retroviral transduction or plasmid transfection with four genes. Unfortunately, viral and plasmid DNA incorporation into chromosomes can lead to disruption of gene transcription and malignant transformation. Tumor formation has been found in offspring of mice generated from blastocysts made mosaic with iPS cells. To proceed with iPS cells for human therapy, reprogramming should be done with transient gene expression. Recently, adenoviral vectors have been used to produce mouse iPS cells without viral integration. Here, we report the successful creation of human iPS cells from embryonic fibroblasts using adenoviral vectors expressing c-Myc, Klf4, Oct4, and Sox2. After screening 12 colonies, three stable iPS cell lines were established. Each cell line showed human embryonic stem cell morphology and surface markers. Southern blots and polymerase chain reaction demonstrated that there was no viral DNA integration into iPS cells. Fingerprinting and karyotype analysis confirmed that these iPS cell lines are derived from the parent human fibroblasts. The three human iPS cell lines can differentiate to all three germ layers in vitro, including dopaminergic neurons. After s.c. injection into nonobese diabetic-severe combined immunodeficient mice, each human iPS line produced teratomas within 5 weeks postimplantation. We conclude that adenoviral vectors can reprogram human fibroblasts to pluripotent stem cells for use in individualized cell therapy without the risk for viral or oncogene incorporation.
File Format	HTM / HTML
ISSN	10665099
Issue Number	11
Volume Number	27
e-ISSN	15494918
Journal	STEM CELLS
Language	English
Publisher	Wiley
Publisher Date	2009-11-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Cell Biology Discipline Embryology Adenoviridae Genetics Fibroblasts Cytology Metabolism Induced Pluripotent Stem Cells Physiology Animals Blotting, Southern Cell Differentiation Cell Line Dna Fingerprinting Genetic Vectors Humans Transplantation Karyotyping Kruppel-like Transcription Factors Mice Mice, Inbred Nod Mice, Scid Octamer Transcription Factor-3 Proto-oncogene Proteins C-myc Reverse Transcriptase Polymerase Chain Reaction Soxb1 Transcription Factors Teratoma Pathology Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine Molecular Medicine

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