Stem Cell Transplantation and Gene Therapy in utero

Abstract

Background: Allogeneic hematopoietic stem cell transplantation in utero has been successfully used for the prenatal treatment of severe combined immunodeficiency syndrome. However, this therapy has not been successful in the treatment of other conditions in which the fetus is immunologically competent. Material and Methods: We reviewed the currently explored strategies to overcome these problems, including prenatal gene therapy using ex vivo transduced autologous hematopoietic cells or direct gene targeting in utero. Results: Some of the strategies such as stromal cell co-transplantation have been shown to be successful in preclinical studies. Similarly, prenatal gene transfer has been shown to be feasible in the fetal sheep model; however, safety concerns regarding transduction of fetal germ cells or maternal cells remain. Conclusion: Progress is being made in the exploration of new modalities of in utero transplantation although the procedure remains experimental and long-term clinical efficacy needs to be proven. In utero gene therapy seems feasible, but more animal studies are needed in order to assess its safety.