Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential.
When mature adipocytes are subjected to an in vitro dedifferentiation strategy referred to as ceiling culture, these mature adipocytes can revert to a more primitive phenotype and gain cell proliferative ability. We refer to these cells as dedifferentiated fat (DFAT) cells. In the present study, we examined the multilineage differentiation potential of DFAT cells. DFAT cells obtained from adipose tissues of 18 donors exhibited a fibroblast-like morphology and sustained high proliferative activity. Flow cytometric analysis revealed that DFAT cells comprised a highly homogeneous cell population compared with that of adipose-derived stem/stromal cells (ASCs), although the cell-surface antigen profile of DFAT cells was very similar to that of ASCs. DFAT cells lost expression of mature adipocytes marker genes but retained or gained expression of mesenchymal lineage-committed marker genes such as peroxisome proliferator-activated receptor gamma (PPARgamma), RUNX2, and SOX9. In vitro differentiation analysis revealed that DFAT cells could differentiate into adipocytes, chondrocytes, and osteoblasts under appropriate culture conditions. DFAT cells also formed osteoid matrix when implanted subcutaneously into nude mice. In addition, clonally expanded porcine DFAT cells showed the ability to differentiate into multiple mesenchymal cell lineages. These results indicate that DFAT cells represent a type of multipotent progenitor cell. The accessibility and ease of culture of DFAT cells support their potential application for cell-based therapies.
Matsumoto
Taro
T
Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan.
Kano
Koichiro
K
Kondo
Daisuke
D
Fukuda
Noboru
N
Iribe
Yuji
Y
Tanaka
Nobuaki
N
Matsubara
Yoshiyuki
Y
Sakuma
Takahiro
T
Satomi
Aya
A
Otaki
Munenori
M
Ryu
Jyunnosuke
J
Mugishima
Hideo
H
D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D054337:Cell Dedifferentiation; D019070:Cell Lineage; D002469:Cell Separation; D020219:Chondrogenesis; D002999:Clone Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010012:Osteogenesis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
D000954:Antigens, Surface