Download VBWG_CT-05 (4 slides

Cell Therapy in CV Disease:
Newest Evidence
2
Induction of pluripotent stem cells from human
fibroblasts
Transcription factors introduced via retroviral transduction
Study
Takahashi,
2007
Yu,
2007
Yield
(iPS colonies/
106 fibroblasts)
Source of
fibroblasts
Transcription
factors
Adult dermis
Oct3/4, Sox2,
Klf4, c-Myc
~200
Postnatal
foreskin
Oct4, Sox2,
NANOG, Lin28
~95
iPS = induced pluripotent stem cells
Takahashi K et al. Cell. 2007.
Yu J et al. Science. 2007.
3
Evidence for successful reprogramming of
human fibroblasts*
• Morphologic similarities with human embryonic stem
(ES) cells
• Expression of surface antigens found in ES
• Telomerase activity
• Ability to sustain continuous culture
• Expression of pluripotency-associated genes
• Pluripotency demonstrated in vivo via teratoma
formation in mice
*Demonstrated in both studies.
Takahashi K et al. Cell. 2007.
Yu J et al. Science. 2007.
4
Effects of composite transcription factor
modulation of human fibroblasts: Conclusions
• Induced pluripotent stem cells can be generated from
human fibroblasts by retroviral transduction of
transcription factors
• Use of vectors that may integrate into genome,
introducing mutations, precludes any clinical
application at present
Takahashi K et al. Cell. 2007.
Yu J et al. Science. 2007.