PMID- 19621077
OWN - NLM
STAT- MEDLINE
DCOM- 20091110
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 7
DP  - 2009 Jul 21
TI  - Self-contained induction of neurons from human embryonic stem cells.
PG  - e6318
LID - 10.1371/journal.pone.0006318 [doi]
LID - e6318
AB  - BACKGROUND: Neurons and glial cells can be efficiently induced from mouse 
      embryonic stem (ES) cells in a conditioned medium collected from rat 
      primary-cultured astrocytes (P-ACM). However, the use of rodent primary cells for 
      clinical applications may be hampered by limited supply and risk of contamination 
      with xeno-proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed an 
      alternative method for unimpeded production of human neurons under xeno-free 
      conditions. Initially, neural stem cells in sphere-like clusters were induced 
      from human ES (hES) cells after being cultured in P-ACM under free-floating 
      conditions. The resultant neural stem cells could circumferentially proliferate 
      under subsequent adhesive culture, and selectively differentiate into neurons or 
      astrocytes by changing the medium to P-ACM or G5, respectively. These hES 
      cell-derived neurons and astrocytes could procure functions similar to those of 
      primary cells. Interestingly, a conditioned medium obtained from the hES 
      cell-derived astrocytes (ES-ACM) could successfully be used to substitute P-ACM 
      for induction of neurons. Neurons made by this method could survive in mice brain 
      after xeno-transplantation. CONCLUSION/SIGNIFICANCE: By inducing astrocytes from 
      hES cells in a chemically defined medium, we could produce human neurons without 
      the use of P-ACM. This self-serving method provides an unlimited source of human 
      neural cells and may facilitate clinical applications of hES cells for 
      neurological diseases.
FAU - Okuno, Tsuyoshi
AU  - Okuno T
AD  - Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, 
      Osaka, Japan.
FAU - Nakayama, Takashi
AU  - Nakayama T
FAU - Konishi, Nae
AU  - Konishi N
FAU - Michibata, Hideo
AU  - Michibata H
FAU - Wakimoto, Koji
AU  - Wakimoto K
FAU - Suzuki, Yutaka
AU  - Suzuki Y
FAU - Nito, Shinji
AU  - Nito S
FAU - Inaba, Toshio
AU  - Inaba T
FAU - Nakano, Imaharu
AU  - Nakano I
FAU - Muramatsu, Shin-Ichi
AU  - Muramatsu S
FAU - Takano, Makoto
AU  - Takano M
FAU - Kondo, Yasushi
AU  - Kondo Y
FAU - Inoue, Nobuo
AU  - Inoue N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090721
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (DNA Primers)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Differentiation
MH  - Culture Media, Conditioned
MH  - DNA Primers
MH  - Electroporation
MH  - Embryonic Stem Cells/*cytology
MH  - Humans
MH  - Mice
MH  - Neurons/*cytology
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stem Cell Transplantation
PMC - PMC2708355
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/07/22 09:00
MHDA- 2009/11/11 06:00
PMCR- 2009/07/21
CRDT- 2009/07/22 09:00
PHST- 2008/06/03 00:00 [received]
PHST- 2009/06/24 00:00 [accepted]
PHST- 2009/07/22 09:00 [entrez]
PHST- 2009/07/22 09:00 [pubmed]
PHST- 2009/11/11 06:00 [medline]
PHST- 2009/07/21 00:00 [pmc-release]
AID - 08-PONE-RA-04934R3 [pii]
AID - 10.1371/journal.pone.0006318 [doi]
PST - epublish
SO  - PLoS One. 2009 Jul 21;4(7):e6318. doi: 10.1371/journal.pone.0006318.