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Prepublished online as a Blood First Edition Paper on April 30, 2002; DOI 10.1182/blood-2002-01-0016. This Article Full Text (PDF) All Versions of this Article: 2002-01-0016v1 100/3/804    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flake, A. W Articles by Shaaban, A. F Search for Related Content PubMed PubMed Citation Articles by Flake, A. W Articles by Shaaban, A. F Social Bookmarking                   What's this? Submitted January 3, 2002 Accepted April 2, 2002 Complete Allogeneic Hematopoietic Chimerism Achieved by a Combined Strategy of In Utero Hematopoietic Stem Cell Transplantation and Postnatal Donor Lymphocyte Infusion Alan W Flake*, Satoshi Hayashi, William H Peranteau, and Aimen F Shaaban The Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, Philadelphia, PA, USA * Corresponding author; email: flake{at}email.chop.edu. In utero hematopoietic stem cell transplantation (IUHSCTx) can achieve mixed hematopoietic chimerism and donor specific tolerance without cytoreductive conditioning or immunosuppression. The primary limitation to clinical application of IUHSCTx has been minimal donor cell engraftment, well below therapeutic levels for most target diseases. Donor lymphocyte infusion (DLI) has been utilized in postnatal circumstances of mixed chimerism as targeted immunotherapy to achieve a graft versus hematopoietic effect and increase levels of donor cell engraftment. In this report we demonstrate in the murine model that a combined approach of IUHSCTx followed by postnatal DLI can convert low level mixed hematopoietic chimerism to complete donor chimerism across full MHC barriers with minimal risk of graft versus host disease. Time-dated E14-15 Balb/c (H2-Kd, CD45.2) fetuses underwent intraperitoneal injection of 5 x 106 T-cell depleted B6 (H2-Kb, CD45.2) BM cells. Chimeric recipients were then transplanted at either 4 or 8 weeks of age with one of three doses (5, 15, or 30 x 106 cells) of donor congenic splenocytes (B6-Ly5.2/Cr, H2- Kb, CD45.1). The response to DLI was dose dependent with conversion to complete donor peripheral blood chimerism in 100% of animals that received high dose (30 x 106 cells) DLI with only 1 of 56 animals receiving this dose succumbing to GVHD. This study directly supports the potential therapeutic strategy of prenatal tolerance induction to facilitate non-toxic postnatal cellular therapy and organ transplantation, and has broad implications for the potential treatment of prenatally diagnosed genetic disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Panaroni, R. Gioia, A. Lupi, R. Besio, S. A. Goldstein, J. Kreider, S. Leikin, J. C. Vera, E. L. Mertz, E. Perilli, et al. In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta Blood, July 9, 2009; 114(2): 459 - 468. [Abstract] [Full Text] [PDF] E. T. Durkin, K. A. Jones, D. Rajesh, and A. F. Shaaban Early chimerism threshold predicts sustained engraftment and NK-cell tolerance in prenatal allogeneic chimeras Blood, December 15, 2008; 112(13): 5245 - 5253. [Abstract] [Full Text] [PDF] P. Fiorina, M. Jurewicz, K. Tanaka, N. Behazin, A. Augello, A. Vergani, U. Von Adrian, N. R. Smith, M. H. Sayegh, and R. Abdi Characterization of Donor Dendritic Cells and Enhancement of Dendritic Cell Efflux With cc-Chemokine Ligand 21: A Novel Strategy to Prolong Islet Allograft Survival Diabetes, April 1, 2007; 56(4): 912 - 920. [Abstract] [Full Text] [PDF] W. H. Peranteau, M. Endo, O. O. Adibe, and A. W. Flake Evidence for an immune barrier after in utero hematopoietic-cell transplantation Blood, February 1, 2007; 109(3): 1331 - 1333. [Abstract] [Full Text] [PDF] W. H. Peranteau, M. Endo, O. O. Adibe, A. Merchant, P. W. Zoltick, and A. W. 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