title: Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation.
abstract: The concept of reprogramming of somatic cells has opened a new era in regenerative medicine. Transduction of defined factors has successfully achieved pluripotency. However, during the generation process of induced pluripotent stem (iPS) cells, genetic manipulation of certain factors may cause tumorigenicity, which limits further application. We report that that a single transfer of embryonic stem (ES) cell-derived proteins into primarily cultured adult mouse fibroblasts, rather than repeated transfer or prolonged exposure to materials, can achieve full reprogramming up to the pluripotent state without the forced expression of ectopic transgenes. During the process, gene expression and epigenetic status were converted from somatic to ES-equivalent status. We verified that protein-based reprogramming was neither by the contamination of protein donor ES cell nor by DNA/RNA from donor ES cell. Protein-iPS cells were biologically and functionally very similar to ES cells and differentiated into 3 germ layers in vitro. Furthermore, protein-iPS cells possessed in vivo differentiation (well-differentiated teratoma formation) and development (chimeric mice generation and a tetraploid blastocyst complementation) potentials. Our results provide an alternative and safe strategy for the reprogramming of somatic cells that can be used to facilitate pluripotent stem cell-based cell therapy.
authors.affiliation: National Research Laboratory for Cardiovascular Stem Cell, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hyun-Jai
authors.initials: HJ
authors.lastname: Cho
authors.forename: Choon-Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Yoo-Wook
authors.initials: YW
authors.lastname: Kwon
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Paek
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin
authors.initials: J
authors.lastname: Hur
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Roh
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Chu
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Leem
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Kang
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Park
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D054337:Cell Dedifferentiation / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D019175:DNA Methylation; D004624:Embryo Transfer; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011506:Proteins / Q000008:administration & dosage* / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; D012333:RNA, Messenger; D000469:Alkaline Phosphatase