Functional recapitulation of smooth muscle cells via induced pluripotent stem cells from human aortic smooth muscle cells.
BACKGROUND
Generation of induced pluripotent stem (iPS) cells has been intensively studied by a variety of reprogramming methods, but the molecular and functional properties of the cells differentiated from iPS cells have not been well characterized.


OBJECTIVE
To address this issue, we generated iPS cells from human aortic vascular smooth muscle cells (HASMCs) using lentiviral transduction of defined transcription factors and differentiated these iPS cells back into smooth muscle cells (SMCs).


RESULTS
Established iPS cells were shown to possess properties equivalent to human embryonic stem cells, in terms of the cell surface markers, global mRNA and microRNA expression patterns, epigenetic status of OCT4, REX1, and NANOG promoters, and in vitro/in vivo pluripotency. The cells were differentiated into SMCs to enable a direct, comparative analysis with HASMCs, from which the iPS cells originated. We observed that iPS cell-derived SMCs were very similar to parental HASMCs in gene expression patterns, epigenetic modifications of pluripotency-related genes, and in vitro functional properties. However, the iPS cells still expressed a significant amount of lentiviral transgenes (OCT4 and LIN28) because of partial gene silencing.


CONCLUSIONS
Our study reports, for the first time, the generation of iPS cells from HASMCs and their differentiation into SMCs. Moreover, a parallel comparative analysis of human iPS cell-derived SMCs and parental HASMCs revealed that iPS-derived cells possessed representative molecular and in vitro functional characteristics of parental HASMCs, suggesting that iPS cells hold great promise as an autologous cell source for patient-specific cell therapy.
Lee
Tae-Hee
TH
Department of Molecular and Life Science, CHA Stem Cell Institute, Pochon CHA University, Seoul, Korea. thlee14@yonsei.ac.kr
Song
Sun-Hwa
SH
Kim
Koung Li
KL
Yi
Ji-Yeun
JY
Shin
Ga-Hee
GH
Kim
Ji Yeon
JY
Kim
Jihoon
J
Han
Yong-Mahn
YM
Lee
Sang Hun
SH
Lee
Suk-Ho
SH
Shim
Sung Han
SH
Suh
Wonhee
W
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016086:Lentivirus; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic
D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; C000715187:Lin28A protein, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C507976:ZFP42 protein, human