Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells.
Hepatocytes generated from human induced pluripotent stem cells (hiPSCs) are unprecedented resources for pharmaceuticals and cell therapy. However, the in vitro directed differentiation of human pluripotent stem cells into mature hepatocytes remains challenging. Little attention has so far been paid to variations among hiPSC lines in terms of their hepatic differentiation. In the current study, we developed an improved hepatic differentiation protocol and compared 28 hiPSC lines originated from various somatic cells and derived using retroviruses, Sendai viruses, or episomal plasmids. This comparison indicated that the origins, but not the derivation methods, may be a major determinant of variation in hepatic differentiation. The hiPSC clones derived from peripheral blood cells consistently showed good differentiation efficiency, whereas many hiPSC clones from adult dermal fibroblasts showed poor differentiation. However, when we compared hiPSCs from peripheral blood and dermal fibroblasts from the same individuals, we found that variations in hepatic differentiation were largely attributable to donor differences, rather than to the types of the original cells. These data underscore the importance of donor differences when comparing the differentiation propensities of hiPSC clones.
Center for Induced Pluripotent Stem Cell Research and Application, Department of Surgery, Graduate School of Medicine, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Masatoshi
M
Kajiwara
Takashi
T
Aoi
Keisuke
K
Okita
Ryosuke
R
Takahashi
Haruhisa
H
Inoue
Naoya
N
Takayama
Hiroshi
H
Endo
Koji
K
Eto
Junya
J
Toguchida
Shinji
S
Uemoto
Shinya
S
Yamanaka
D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008297:Male