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Title: In vitro modeling of paraxial mesodermal progenitors derived from induced pluripotent stem cells.
Authors: Sakurai, Hidetoshi  kyouindb  KAKEN_id
Sakaguchi, Yasuko
Shoji, Emi
Nishino, Tokiko
Maki, Izumi
Sakai, Hiroshi
Hanaoka, Kazunori
Kakizuka, Akira  kyouindb  KAKEN_id
Sehara-Fujisawa, Atsuko
Author's alias: 櫻井, 英俊
Issue Date: 24-Oct-2012
Publisher: Public Library of Science
Journal title: PloS one
Volume: 7
Issue: 10
Thesis number: e47078
Abstract: Induced pluripotent stem (iPS) cells are generated from adult somatic cells by transduction of defined factors. Given their unlimited proliferation and differentiation potential, iPS cells represent promising sources for cell therapy and tools for research and drug discovery. However, systems for the directional differentiation of iPS cells toward paraxial mesodermal lineages have not been reported. In the present study, we established a protocol for the differentiation of mouse iPS cells into paraxial mesodermal lineages in serum-free culture. The protocol was dependent on Activin signaling in addition to BMP and Wnt signaling which were previously shown to be effective for mouse ES cell differentiation. Independently of the cell origin, the number of transgenes, or the type of vectors used to generate iPS cells, the use of serum-free monolayer culture stimulated with a combination of BMP4, Activin A, and LiCl enabled preferential promotion of mouse iPS cells to a PDGFR-α(+)/Flk-1(-) population, which represents a paraxial mesodermal lineage. The mouse iPS cell-derived paraxial mesodermal cells exhibited differentiation potential into osteogenic, chondrogenic, and myogenic cells both in vitro and in vivo and contributed to muscle regeneration. Moreover, purification of the PDGFR-α(+)/KDR(-) population after differentiation allowed enrichment of human iPS cell populations with paraxial mesodermal characteristics. The resultant PDGFR-α(+)/KDR(-) population derived from human iPS cells specifically exhibited osteogenic, chondrogenic, and myogenic differentiation potential in vitro, implying generation of paraxial mesodermal progenitors similar to mouse iPS cell-derived progenitors. These findings highlight the potential of protocols based on the serum-free, stepwise induction and purification of paraxial mesodermal cell lineages for use in stem cell therapies to treat diseased bone, cartilage, and muscle.
Rights: © 2012 Sakurai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/2433/161766
DOI(Published Version): 10.1371/journal.pone.0047078
PubMed ID: 23115636
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