In utero hematopoietic stem cell transfer: current status and future strategies

• Published in: European journal of obstetrics & gynecology and reproductive biology 1999-07, Vol.85 (1), p.109-115
• Main Authors: Surbek, Daniel V, Gratwohl, Alois, Holzgreve, Wolfgang
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Female; Fetal Diseases - therapy; Fetal therapy; Genetic Therapy; Hematopoietic Stem Cell Transplantation - trends; Hematopoietic stem cells; Hemoglobinopathies - therapy; Humans; Immunologic Deficiency Syndromes - therapy; In utero transplantation; Medical sciences; Metabolism, Inborn Errors - therapy; Pregnancy; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0301-2115; 1872-7654
• DOI: 10.1016/S0301-2115(98)00293-0

Successful prenatal treatment of severe immunodeficiencies by allogeneic hematopoietic stem cell transplantation in utero has been reported. Though other diseases like hemoglobinopathies or storage diseases are potentially amenable to this novel therapeutic approach, no success has yet been achieved in recipients without severe immunodeficiency. Graft rejection by the developing fetus and/or lack of selective, competitive advantage of donor versus host stem cells preventing stable engraftment seem to be the major obstacles. Several strategies to overcome these hurdles are being explored in preclinical settings, including timing and repeated dosing of stem cell administration to the fetus, ex vivo modification of the transplant, using different fetal compartments as targets for early stem cell transfer, or inducing microchimerism for postnatal transplantation from the same donor. In addition, the exact definition of the basic concept of early fetal immunologic naiveté and the understanding of the molecular basics of migration and homing in fetal hematopoiesis system seem mandatory for a successful approach. Gene therapy using ex vivo transduced autologous cord blood cells or direct gene targeting in utero are other potential means to correct hematopoietic and immunologic single gene disorders in utero, though this approach is still away from the stage of clinical trials.