In utero transplantation of autologous and allogeneic fetal liver stem cells in ovine fetuses Andreina Schoeberlein, PhD, Wolfgang Holzgreve, MD, MS, Lisbeth Dudler, Sinuhe Hahn, PhD, Daniel V. Surbek, MD * University Women’s Hospital/Department of Research, University of Basel, Switzerland KEY WORDS In utero transplantation Stem cell Autologous Allogeneic Sheep Objective: The purpose of this study was to assess the feasibility of autologous stem cell transplantation in fetal sheep and to compare short-term engraftment of allogeneic and autologous fetal liver stem cells in an immunocompetent large animal model. Study design: Fetal liver stem cells were collected from preimmune sheep fetuses with an open or ultrasound-guided technique. After being labeled with PKH26, the cells were transplanted intraperitoneally into allogeneic and autologous fetal recipients at 48 to 64 days of gestation. Engraftment was determined by flow cytometry and real-time polymerase chain reaction 1 to 2 weeks after transplantation. Results: Fetal loss rate was 29% (allogeneic transplantation) and 73% (autologous trans- plantation). Engraftment of donor cells was found in all fetuses, with a level of %4.7% in fetal liver, spleen, bone marrow, blood and thymus. Overall, there was no difference between allogeneic and autologous grafts. Conclusion: Autologous in utero transplantation of fetal liver stem cells in fetal sheep is feasible, but yields a high loss rate. Differences in the major histocompatibility complex between donor and recipient seems not to have a major impact on stem cell engraftment early in gestation; major histocompatibility complexeindependent donor/host competition might be responsible for low engraftment in immunocompetent recipients. Ó 2004 Elsevier Inc. All rights reserved. Transplantation of stem cells in the affected child is an efficient treatment for a number of genetic disorders, but it is limited because of a lack of available stem cell graft and treatment-associated morbidity. In utero stem cell transplantation (IUTx) is a prom- ising potential therapy for a number of these disorders and has several potential advantages over postnatal treatment. It has the potential for the prevention of progressive irreversible damage to the fetus during its development. 1 The rationale for transplantation of stem cells to the fetus is based on two main assumptions: First, the immature fetal immune system has not the full competence to discriminate between ‘‘self’’ and ‘‘non- self’’ and is unable to drive an adequate immune response against foreign donor cells, which obviates the need for major histocompatibility complex (MHC)ematching. 2 Second, the rapidly developing Supported by the Swiss National Science Foundation NFP46 grant No. 4046-058662/1. Presented at the Twenty-Fourth Annual Meeting of the Society for Maternal Fetal Medicine, New Orleans, La, February 2-7, 2004. * Reprint requests: Daniel Surbek, MD, Department of Obstetrics and Gynecology, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland. E-mail: surbek@hotmail.com 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.06.042 American Journal of Obstetrics and Gynecology (2004) 191, 1030e6 www.elsevier.com/locate/ajog