Induction of pluripotency in human cord blood unrestricted somatic stem cells.
OBJECTIVE
Generation of induced pluripotent stem (iPS) cells from human cord blood (CB)-derived unrestricted somatic stem cells and evaluation of their molecular signature and differentiation potential in comparison to human embryonic stem cells.


METHODS
Unrestricted somatic stem cells isolated from human CB were reprogrammed to iPS cells using retroviral expression of the transcription factors OCT4, SOX2, KLF4, and C-MYC. The reprogrammed cells were analyzed morphologically, by quantitative reverse transcription polymerase chain reaction, genome-wide microRNA and methylation profiling, and gene expression microarrays, as well as in their pluripotency potential by in vivo teratoma formation in severe combined immunodeficient mice and in vitro differentiation.


RESULTS
CB iPS cells are very similar to human embryonic stem cells morphologically, at their molecular signature, and in their differentiation potential.


CONCLUSIONS
Human CB-derived unrestricted somatic stem cells offer an attractive source of cells for generation of iPS cells. Our findings open novel perspectives to generate human leukocyte antigen-matched pluripotent stem cell banks based on existing CB banks. Besides the obvious relevance of a second-generation CB iPS cell bank for pharmacological and toxicological testing, its application for autologous or allogenic regenerative cell transplantation appears feasible.
Zaehres
Holm
H
Max Planck Institute for Molecular Biomedicine, Münster, Germany.
Kögler
Gesine
G
Arauzo-Bravo
Marcos J
MJ
Bleidissel
Martina
M
Santourlidis
Simeon
S
Weinhold
Sandra
S
Greber
Boris
B
Kim
Jeong Beom
JB
Buchheiser
Anja
A
Liedtke
Stefanie
S
Eilken
Hanna M
HM
Graffmann
Nina
N
Zhao
Xiaoyi
X
Meyer
Johann
J
Reinhardt
Peter
P
Burr
Boris
B
Waclawczyk
Simon
S
Ortmeier
Claudia
C
Uhrberg
Markus
M
Schöler
Hans R
HR
Cantz
Tobias
T
Wernet
Peter
P
D000818:Animals; D054337:Cell Dedifferentiation; D019175:DNA Methylation / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism*; D055106:Genome-Wide Association Study; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013724:Teratoma / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D035683:MicroRNAs; D014157:Transcription Factors