title: Migration of cells from the yolk sac to hematopoietic tissues after in utero transplantation of early and mid gestation canine fetuses.
abstract: BACKGROUND
  In utero hematopoietic cell transplantation offers a means of early intervention for the treatment of diseases before birth. Delivery of cells to the yolk sac is a minimally invasive approach that results in low levels of chimerism. However, there is little information on the optimal doses, timing of delivery, and migration of transplanted cells from the yolk sac into the fetus.
  
  
  METHODS
  Varying cell doses of mesenchymal stromal cells or bone marrow mononuclear cells labeled with fluorescent supraparamagnetic iron oxide nanoparticles and a fluorescent intracellular dye, 5- and 6-([(4-chloromethyl)benzoyl]-amino) tetramethylrhodamine, were transplanted under ultrasound guidance to the yolk sacs of day 25 or day 35 canine fetuses. Ex vivo whole body fluorescence imaging and microscopy of tissue sections were correlated with the presence of iron oxide in injected and control fetuses.
  
  
  RESULTS
  Day 25 and day 35 recipients showed similar survival rates after injection of cells into yolk sacs, although increased fetal morality was associated with cell doses greater than 10 cells/kg to day 25 fetuses. The fluorescence and iron oxide signals were predominantly localized to the abdominal regions, with no fluorescence visible in yolk sacs. Microscopy of tissues revealed colocalization of fluorophore with iron oxide in donor cells detected in the fetal livers and bone marrow of recipients 7 and 17 days after receiving mesenchymal stromal cells or bone marrow mononuclear cells.
  
  
  CONCLUSIONS
  These studies demonstrated that cells injected into the yolk sacs of early gestation canine fetuses migrate to recipient hematopoietic tissues. Thus, yolk sac injection offers a safe and effective approach for engraftment of cells to fetal hematopoietic tissues.
authors.affiliation: Department of Molecular and Cellular Biology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Vaags
authors.forename: Cathy J
authors.initials: CJ
authors.lastname: Gartley
authors.forename: Krista B
authors.initials: KB
authors.lastname: Halling
authors.forename: Howard
authors.initials: H
authors.lastname: Dobson
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Zheng
authors.forename: Warren D
authors.initials: WD
authors.lastname: Foltz
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Dick
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Kruth
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Hough
mesh_terms: D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D004285:Dogs; D005260:Female; D005315:Fetal Diseases / Q000628:therapy*; D046689:Fetal Mortality; D005453:Fluorescence; D005865:Gestational Age; D018380:Hematopoietic Stem Cell Transplantation; D058185:Magnetite Nanoparticles; D011247:Pregnancy; D012235:Rhodamines / Q000378:metabolism; D015017:Yolk Sac / Q000166:cytology*
chemical_list: C116572:(((4-chloromethyl)benzoyl)amino)-tetramethylrhodamine; D058185:Magnetite Nanoparticles; D012235:Rhodamines