title: Engraftment and tumor formation after allogeneic in utero transplantation of primate embryonic stem cells.
abstract: BACKGROUND
  To achieve human embryonic stem (ES) cell-based transplantation therapies, allogeneic transplantation models of nonhuman primates would be useful. We have prepared cynomolgus ES cells genetically marked with the green fluorescent protein (GFP). The cells were transplanted into the allogeneic fetus, taking advantage of the fact that the fetus is so immunologically immature as not to induce immune responses to transplanted cells and that fetal tissue compartments are rapidly expanding and thus providing space for the engraftment.
  
  
  METHODS
  Cynomolgus ES cells were genetically modified to express the GFP gene using a simian immunodeficiency viral vector or electroporation. These cells were transplanted in utero with ultrasound guidance into the cynomolgus fetus in the abdominal cavity (n=2) or liver (n=2) at the end of the first trimester. Three fetuses were delivered 1 month after transplantation, and the other, 3 months after transplantation. Fetal tissues were examined for transplanted cell progeny by quantitative polymerase chain reaction and in situ polymerase chain reaction of the GFP sequence.
  
  
  RESULTS
  A fluorescent tumor, obviously derived from transplanted ES cells, was found in the thoracic cavity at 3 months after transplantation in one fetus. However, transplanted cell progeny were also detected (approximately 1%) without teratomas in multiple fetal tissues. The cells were solitary and indistinguishable from surrounding host cells.
  
  
  CONCLUSIONS
  Transplanted cynomolgus ES cells can be engrafted in allogeneic fetuses. The cells will, however, form a tumor if they "leak" into an improper space such as the thoracic cavity.
authors.affiliation: Division of Genetic Therapeutics, Jichi Medical School, Tochigi, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asano
authors.forename: Naohide
authors.initials: N
authors.lastname: Ageyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Mikio
authors.initials: M
authors.lastname: Momoeda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kitano
authors.forename: Kyoko
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kondo
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Torii
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ookawara
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Harii
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hanazono
mesh_terms: D000818:Animals; D005260:Female; D005333:Fetus; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000493:pharmacokinetics; D008252:Macaca fascicularis; D008297:Male; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D013899:Thoracic Neoplasms / Q000209:etiology*; D013997:Time Factors; D014184:Transplantation, Homologous; D014599:Uterus / Q000601:surgery*
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins