Tissue-specific engraftment after in utero transplantation of allogeneic mesenchymal stem cells into sheep fetuses.
OBJECTIVE
Mesenchymal stem cells (MSC) have multiorgan differentiation capacity, providing the potential for prenatal treatment of genetic disorders. We address the question if in utero transplantation of MSC results in short-term organ-specific engraftment in the fetal sheep.


METHODS
Sheep fetal liver-derived MSC selected by adherence culture (passage 1) were transplantated into the fetal peritoneal cavity with ultrasound-guidance (mean gestational age, 59 days). After 14 days recipient fetuses were analyzed by fluorescence-activated cell sorting (FACS), real-time polymerase chain reaction (PCR), and immunohistochemistry.


RESULTS
Fetuses (n = 11) were transplanted with 7.7 x 10(6) MSCs (mean). All surviving fetuses (n = 5) showed engraftment with mean levels of 3.2% (lung), 0.8% (spleen), 0.6% (liver, brain), 0.4% (bone marrow), 0.1% (blood, thymus), and <0.1% (kidneys) by flow cytometry. Immunohistochemistry showed organ-specific distribution.


CONCLUSIONS
In utero transplantation of allogeneic MSC results in low level, multiorgan engraftment at 14 days post transplant. This supports the potential of in utero MSC transplantation for the treatment of nonhematopoietic genetic disorders of the fetus.
Schoeberlein
Andreina
A
University Women's Hospital, Department of Research, University of Basel, Basel, Switzerland.
Holzgreve
Wolfgang
W
Dudler
Lisbeth
L
Hahn
Sinuhe
S
Surbek
Daniel V
DV
D000818:Animals; D000013:Congenital Abnormalities / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D006084:Graft Rejection; D006085:Graft Survival; D022781:Hepatocytes / Q000637:transplantation*; D059630:Mesenchymal Stem Cells; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D012680:Sensitivity and Specificity; D034561:Sheep, Domestic; D033581:Stem Cell Transplantation / Q000379:methods*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous