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Although successful in utero hematopoietic cell transplantation (IUHCT) of X-linked severe combined immune deficiency (X-SCID) with enriched stem and progenitor cells was achieved more than a decade ago, it remains applied only in rare cases. Although this in part reflects that postnatal transplantations have overall given good results, there are no direct comparisons between IUHCT and postnatal transplantations of X-SCID. The proposed tolerance of the fetal immune system to foreign human leukocyte antigen early in gestation, a main rationale behind IUHCT, has recently been challenged by evidence for a considerable immune barrier against in utero transplanted allogeneic bone marrow cells. Consequently, there is need for further exploring the application of purified stem and progenitor cells to overcome this barrier also in IUHCT. Herein, we demonstrate in a congenic setting that recently identified lymphoid-primed multipotent progenitors are superior to hematopoietic stem cells in providing rapid lymphoid reconstitution after IUHCT of X-SCID recipients, and sustain in the long-term B cells, polyclonal T cells, as well as short-lived B-cell progenitors and thymic T-cell precursors. We further provide evidence for IUHCT of hematopoietic stem cells giving superior B- and T-cell reconstitution in fetal X-SCID recipients compared with neonatal and adolescent recipients.

Original publication

DOI

10.1182/blood-2007-12-129056

Type

Journal article

Journal

Blood

Publication Date

07/05/2009

Volume

113

Pages

4790 - 4798

Keywords

Animals, Animals, Newborn, Bone Marrow, Female, Fetus, Gene Rearrangement, Hematopoietic Stem Cells, Lymphoid Progenitor Cells, Lymphopoiesis, Mice, Mice, Inbred C57BL, Mice, SCID, Multipotent Stem Cells, Myeloid Cells, Stem Cells, T-Lymphocytes, Thymus Gland, Uterus, X-Linked Combined Immunodeficiency Diseases