Wednesday, November 03, 2010
stem cells
Authors
Luigi Warren, Philip D. Manos, Tim Ahfeldt, Yuin-Han Loh, Hu Li, Frank Lau, Wataru Ebina, Pankaj K. Mandal, Zachary D. Smith, Alexander Meissner, George Q. Daley, Andrew S. Brack, James J. Collins, Chad Cowan, Thorsten M. Schlaeger, Derrick J. RossiSee AffiliationsHint: Rollover Authors and Affiliations Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115, USA Stem Cell Program, Children's Hospital Boston, Boston, MA 02115, USA Manton Center for Orphan Disease Research, Children's Hospital Boston, Boston, MA 02115, USA Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Center of Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114-2790, USA Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA Department of Pathology, Harvard Medical School, Boston, MA 02115, USA Department of Biomedical Engineering and Center for BioDynamics, Boston University, Boston, MA 02215, USA Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA Stowers Medical Institute, 185 Cambridge Street, Boston, MA 02114, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Howard Hughes Medical Institute Division of Hematology/Oncology, Brigham and Women's Hospital, Boston, MA 02115, USA Corresponding author These authors contributed equally to this work
Highlights
•Modified mRNAs can express reprogramming proteins and evade antiviral response
•Highly efficient derivation of human iPSCs without genomic integration
•RNA-derived iPSCs faithfully recapitulate the properties of human ESCs
•Efficient directed differentiation of iPSCs to differentiated myotubes
Summary
Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.
Luigi Warren, Philip D. Manos, Tim Ahfeldt, Yuin-Han Loh, Hu Li, Frank Lau, Wataru Ebina, Pankaj K. Mandal, Zachary D. Smith, Alexander Meissner, George Q. Daley, Andrew S. Brack, James J. Collins, Chad Cowan, Thorsten M. Schlaeger, Derrick J. RossiSee AffiliationsHint: Rollover Authors and Affiliations Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115, USA Stem Cell Program, Children's Hospital Boston, Boston, MA 02115, USA Manton Center for Orphan Disease Research, Children's Hospital Boston, Boston, MA 02115, USA Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Center of Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114-2790, USA Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA Department of Pathology, Harvard Medical School, Boston, MA 02115, USA Department of Biomedical Engineering and Center for BioDynamics, Boston University, Boston, MA 02215, USA Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA Stowers Medical Institute, 185 Cambridge Street, Boston, MA 02114, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Howard Hughes Medical Institute Division of Hematology/Oncology, Brigham and Women's Hospital, Boston, MA 02115, USA Corresponding author These authors contributed equally to this work
Highlights
•Modified mRNAs can express reprogramming proteins and evade antiviral response
•Highly efficient derivation of human iPSCs without genomic integration
•RNA-derived iPSCs faithfully recapitulate the properties of human ESCs
•Efficient directed differentiation of iPSCs to differentiated myotubes
Summary
Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.
# posted by roodbont @ 1:50 AM 
