title: In vitro characterization and engraftment of adipocytes derived from human induced pluripotent stem cells and embryonic stem cells.
abstract: Human induced pluripotent stem (iPS) and embryonic stem (ES) cells can differentiate into a variety of cell types. We reported on adipogenic potential of human iPS and ES cells in vitro. In the present study, we investigate the survival and maintenance of adipocytes differentiated in vitro from human iPS and ES cells after transplantation. Following adipogenic induction in vitro, the differentiated cells exhibited functional properties of adipocytes such as lipid storage, lipolysis, and insulin responsiveness. Subsequently, Matrigel containing the differentiated human iPS and ES cells was transplanted into the subcutaneous tissue of nude mice. After 1-4 weeks, the cells with adipocyte-like features were observed in transplanted Matrigel by histological analysis. The human origin of the cells, their lipid accumulation, and gene expression of adipocyte markers in transplanted cells were then confirmed, suggesting the presence of adipocytes in transplanted Matrigel. When the relative areas of these cells were calculated by dividing the adipocyte areas by the total Matrigel areas, we found that they peaked at 2 weeks after transplantation, and that the adipocytes persisted at 4 weeks. The present study demonstrates that human iPS and ES cells can differentiate into adipocytes with functional properties and that adipocytes derived from human iPS and ES cells can survive and maintain the differentiated properties of adipocytes for at least 4 weeks after transplantation. Adipocytes derived from human iPS and ES cells thus have the potential to open new avenues for stem cell-based research into metabolic diseases and future therapeutic applications.
authors.affiliation: 1 Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto University , Kyoto, Japan .
authors.forename: Michio
authors.initials: M
authors.lastname: Noguchi
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Maiko
authors.initials: M
authors.lastname: Nakane
authors.forename: Eisaku
authors.initials: E
authors.lastname: Mori
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakao
authors.forename: Daisuke
authors.initials: D
authors.lastname: Taura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Sone
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sakurai
authors.forename: Junji
authors.initials: J
authors.lastname: Fujikura
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods; D003094:Collagen; D004338:Drug Combinations; D053595:Embryonic Stem Cells / Q000166:cytology*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007797:Laminin; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D004338:Drug Combinations; D007797:Laminin; D047495:PPAR gamma; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen