In Utero Transplantation of Human Stem Cells Using an Animal Model: A Comparison Between Two Techniques

Abstract


 
 
 Objective: The purpose of this study was to assess the feasibility of in utero stem cell transplantation of human umbilical cord blood stem cells in fetal sheep and to compare two different techniques of in utero transplantation, namely ultrasound-guided in utero transplantation and in utero transplantation after midline celiotomy.
 Study design: Umbilical cord blood units were collected from term deliveries, after obtaining written informed consent. Human cord blood–derived, CD34+ stem cells were injected into the peritoneal cavity of 60- to 65-day-old ovine fetuses by using 2 different techniques: ultrasound-guided transabdominal percutaneous needle puncture and midline celiotomy with the exposure of the pregnant uterus. Engraftment was determined after birth by flow cytometry with use of human-specific anti-CD 34/45 antibodies.
 Results: We obtained a total of 3 chimeric lambs. Using the midline celiotomy technique the fetal loss rate was 75% and only 33,3% when using ultrasound-guided transabdominal percutaneous needle puncture technique. Engraftment of donor cells was found in all fetuses, with a mean level of 1.4% in fetal peripheral blood and 3.3% in fetal bone marrow.
 Conclusion: This preliminary study indicates that in utero stem cell transplantation of human hematopoietic cord blood stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment. We also concluded that the ultrasound-guided transabdominal percutaneous needle puncture technique is more effective than performing a midline celiotomy in terms of fetal loss rate.