Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA

被引：1970

作者：

Warren, Luigi ^{[1
]}

Manos, Philip D. ^{[2
,4
]}

Ahfeldt, Tim ^{[4
,6
,7
]}

Loh, Yuin-Han ^{[8
,9
,10
]}

Li, Hu ^{[12
,13
,14
]}

Lau, Frank ^{[4
,15
]}

Ebina, Wataru ^{[1
]}

Mandal, Pankaj K. ^{[1
]}

Smith, Zachary D. ^{[16
]}

Meissner, Alexander ^{[4
,5
,16
]}

Daley, George Q. ^{[2
,3
,4
,5
,8
,9
,17
,18
]}

Brack, Andrew S. ^{[5
,6
]}

Collins, James J. ^{[12
,13
,14
,17
]}

Cowan, Chad ^{[4
,5
,6
,15
]}

Schlaeger, Thorsten M. ^{[2
,8
,9
]}

Rossi, Derrick J. ^{[1
,2
,5
,11
]}

机构：

[1] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA

[2] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA

[3] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA

[4] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[5] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[6] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[7] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Biol Mol Cell Biol 2, D-20246 Hamburg, Germany

[8] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA

[9] Dana Farber Canc Inst, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[11] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[12] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA

[13] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA

[14] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA

[15] Stowers Med Inst, Boston, MA 02114 USA

[16] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA

[17] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA

[18] Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA

来源：

CELL STEM CELL | 2010年 / 7卷 / 05期

关键词：

TOLL-LIKE RECEPTORS; STEM-CELLS; ANTIVIRAL RESPONSES; IN-VITRO; INDUCTION; VECTOR; FIBROBLASTS; GENERATION; ANTIGEN; VIRUS;

D O I：

10.1016/j.stem.2010.08.012

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：618 / 630

页数：13

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