한빛사논문, 상위피인용논문
Abstract
Hua Liu, Zhaohui Ye, Yonghak Kim, Saul Sharkis, Yoon-Young Jang * †
Johns Hopkins University School of Medicine 1550 Orleans Street, CRB2 Rm552 Baltimore, MD 21231
*Correspondence to Yoon-Young Jang, Johns Hopkins University School of Medicine 1550 Orleans Street, CRB2 Rm552 Baltimore, MD 21231
†Ph: (410)-502-8195
Funded by:
NIH; Grant Number: DK O70971
Maryland Stem Cell Research Fund; Grant Number: #90034362, #90034927
Abstract
Recent advances in induced pluripotent stem (iPS) cell research significantly changed our perspective on regenerative medicine. Patient specific iPS cells have been derived not only for disease modeling but also as sources for cell replacement therapy. However, there have been insufficient data to prove that iPS cells are functionally equivalent to hES cells or safer than hES cells. There are several important issues which need to be addressed and foremost are the safety and efficacy of human iPS cells from different origins. Human iPS cells have been derived mostly from cells originated from mesoderm, with a few cases from ectoderm. So far there has been no report of endoderm derived human iPS cells, preventing comprehensive comparative investigations on the quality of human iPS cells from different origins.
Here we show for the first time reprogramming of human endoderm derived cells (i.e. primary hepatocytes) to pluripotency. Hepatocyte-derived iPS cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, and differentiation potential in embryoid body formation and teratoma assays. In addition, these cells were able to directly differentiate into definitive endoderm, hepatic progenitors, and mature hepatocytes. The technology to develop endoderm derived human iPS cell lines, together with other established cell lines, will provide a foundation to elucidate the mechanisms of cellular reprogramming and to study the safety and efficacy of differentially originated human iPS cells for cell therapy. For studying liver disease pathogenesis, this technology also provides a potentially more amenable system to generate liver disease specific iPS cells. (HEPATOLOGY 2010.)
Received: 23 November 2009; Revised: 2 February 2010; Accepted: 16 February 2010
Digital Object Identifier (DOI)
10.1002/hep.23626
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