title: Sox2 transduction enhances cardiovascular repair capacity of blood-derived mesoangioblasts.
abstract: BACKGROUND
  Complementation of pluripotency genes may improve adult stem cell functions.
  
  
  OBJECTIVE
  Here we show that clonally expandable, telomerase expressing progenitor cells can be isolated from peripheral blood of children. The surface marker profile of the clonally expanded cells is distinct from hematopoietic or mesenchymal stromal cells, and resembles that of embryonic multipotent mesoangioblasts. Cell numbers and proliferative capacity correlated with donor age. Isolated circulating mesoangioblasts (cMABs) express the pluripotency markers Klf4, c-Myc, as well as low levels of Oct3/4, but lack Sox2. Therefore, we tested whether overexpression of Sox2 enhances pluripotency and facilitates differentiation of cMABs in cardiovascular lineages.
  
  
  RESULTS
  Lentiviral transduction of Sox2 (Sox-MABs) enhanced the capacity of cMABs to differentiate into endothelial cells and cardiomyocytes in vitro. Furthermore, the number of smooth muscle actin positive cells was higher in Sox-MABs. In addition, pluripotency of Sox-MABs was shown by demonstrating the generation of endodermal and ectodermal progenies. To test whether Sox-MABs may exhibit improved therapeutic potential, we injected Sox-MABs into nude mice after acute myocardial infarction. Four weeks after cell therapy with Sox-MABs, cardiac function was significantly improved compared to mice treated with control cMABs. Furthermore, cell therapy with Sox-MABs resulted in increased number of differentiated cardiomyocytes, endothelial cells, and smooth muscle cells in vivo.
  
  
  CONCLUSIONS
  The complementation of Sox2 in Oct3/4-, Klf4-, and c-Myc-expressing cMABs enhanced the differentiation into all 3 cardiovascular lineages and improved the functional recovery after acute myocardial infarction.
authors.affiliation: Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Stefan
authors.initials: S
authors.lastname: Rupp
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Tedesco
authors.forename: Chang-Hwan
authors.initials: CH
authors.lastname: Yoon
authors.forename: Jes-Niels
authors.initials: JN
authors.lastname: Boeckel
authors.forename: Janina
authors.initials: J
authors.lastname: Trauth
authors.forename: Corina
authors.initials: C
authors.lastname: Schütz
authors.forename: Kisho
authors.initials: K
authors.lastname: Ohtani
authors.forename: Rebekka
authors.initials: R
authors.lastname: Goetz
authors.forename: Kazuma
authors.initials: K
authors.lastname: Iekushi
authors.forename: Philipp
authors.initials: P
authors.lastname: Bushoven
authors.forename: Stefan
authors.initials: S
authors.lastname: Momma
authors.forename: Christine
authors.initials: C
authors.lastname: Mummery
authors.forename: Robert
authors.initials: R
authors.lastname: Passier
authors.forename: Reinhard
authors.initials: R
authors.lastname: Henschler
authors.forename: Hakan
authors.initials: H
authors.lastname: Akintuerk
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schranz
authors.forename: Carmen
authors.initials: C
authors.lastname: Urbich
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Galvez
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors / Q000235:genetics; D006614:Hindlimb; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000637:transplantation*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000637:transplantation; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000637:transplantation; D018919:Neovascularization, Physiologic; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D036102:Peripheral Blood Stem Cell Transplantation; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012038:Regeneration; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014161:Transduction, Genetic; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors