Directed Differentiation of Human-Induced Pluripotent Stem Cells Generates Active Motor Neurons

Authors


  • Author contributions: S.K.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; B.N.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript, financial support; M.P.: collection and assembly of data, data analysis and interpretation; J.U.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; L.R.: technical support, provision of study material; A.L.: collection and assembly of data; A.C.: collection and assembly of data; A.C.: collection and assembly of data, financial support; S.A.G.: data analysis and interpretation, manuscript writing, final approval of manuscript; K.P.: data analysis and interpretation, manuscript writing, final approval of manuscript; M.W.-P.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript, financial support; H.I.K.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript; W.E.L.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript, and financial support. S.K., B.G.N., M.P. contributed equally to this work. B.G.N., M.W.P., H.I.K., and W.E.L. contributed equally to this work.

  • First published online in STEM CELLSExpress February 23, 2009.

Abstract

The potential for directed differentiation of human-induced pluripotent stem (iPS) cells to functional postmitotic neuronal phenotypes is unknown. Following methods shown to be effective at generating motor neurons from human embryonic stem cells (hESCs), we found that once specified to a neural lineage, human iPS cells could be differentiated to form motor neurons with a similar efficiency as hESCs. Human iPS-derived cells appeared to follow a normal developmental progression associated with motor neuron formation and possessed prototypical electrophysiological properties. This is the first demonstration that human iPS-derived cells are able to generate electrically active motor neurons. These findings demonstrate the feasibility of using iPS-derived motor neuron progenitors and motor neurons in regenerative medicine applications and in vitro modeling of motor neuron diseases. STEM CELLS 2009;27:806–811

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