Amir Alhajjat1, Aimen Shaaban2,3. 1. Division of Pediatric Surgery, Phoenix Children's Hospital, 1919 E Thomas Rd, Phoenix, Arizona. 2. The Chicago Institute for Fetal Health, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. 3. Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Abstract
PURPOSE OF REVIEW: In Utero Hematopoietic Cellular Transplantation (IUHCT) is a promising intervention for the non-toxic treatment of congenital disease that hinges on the assumption of fetal immunologic immaturity and an inability to reject a hematopoietic allograft. However, clinical IUCHT has failed except in cases where the fetus is severely immunocompromised. The current review examines recent studies of engraftment barriers stemming from either the fetal or maternal immune system. RECENT FINDINGS: New reports have illuminated roles for maternal humoral and cellular immunity and fetal innate cellular immunity in the resistance to allogeneic IUHCT. These experimental findings have inspired new approaches to overcome these barriers. Despite these advances, postulates regarding a maternal immune barrier to IUHCT provide an inadequate explanation for the well-documented clinical success only in the treatment of fetal immunodeficiency with normal maternal immunity. SUMMARY: Characterization of the maternal and fetal immune response to allogeneic IUHCT provides new insight into the complexity of prenatal tolerance. Future work in this area should aim to provide a unifying explanation for the observed patterns of success and failure with clinical IUHCT.
PURPOSE OF REVIEW: In Utero Hematopoietic Cellular Transplantation (IUHCT) is a promising intervention for the non-toxic treatment of congenital disease that hinges on the assumption of fetal immunologic immaturity and an inability to reject a hematopoietic allograft. However, clinical IUCHT has failed except in cases where the fetus is severely immunocompromised. The current review examines recent studies of engraftment barriers stemming from either the fetal or maternal immune system. RECENT FINDINGS: New reports have illuminated roles for maternal humoral and cellular immunity and fetal innate cellular immunity in the resistance to allogeneic IUHCT. These experimental findings have inspired new approaches to overcome these barriers. Despite these advances, postulates regarding a maternal immune barrier to IUHCT provide an inadequate explanation for the well-documented clinical success only in the treatment of fetal immunodeficiency with normal maternal immunity. SUMMARY: Characterization of the maternal and fetal immune response to allogeneic IUHCT provides new insight into the complexity of prenatal tolerance. Future work in this area should aim to provide a unifying explanation for the observed patterns of success and failure with clinical IUHCT.
Entities:
Keywords:
Fetal immune system; IUHCT; In utero transplantation; Materno-fetal trafficking; NK cells; Tolerance
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