application) The long term goal of this project is to further elucidate factors that influence engraftment of allogeneic CD34+ hematopoietic stem and progenitor cells (HP/SC) in utero. Postnatal allogeneic bone marrow transplants can cure many heritable diseases that affect HP/SC and lymphohematopoietic progeny. However, this form of therapy requires supralethal doses of radio/chemo therapy and post-transplant immunosuppression to ensure engraftment and prevent graft verses host disease (GVHD). Effective postnatal therapy is also limited by the availability of a suitably HLA matched donor and, if there is an available donor, transplantation is frequently done only after the onset of clinical symptoms. Unfortunately, many disorders produce irreversible organ damage early in life. In utero transplantation of allogeneic HP/SC has the potential to avoid the morbidity and mortality of postnatal therapy. Experiments of nature and experimental animal models suggest that in utero transplantation should be feasible. Successful engraftment of CD34+ and HP/SC from fetal liver cells has been reported in fetuses with immune deficiencies. Unfortunately, it is unclear if in utero transplantation of immunologically normal fetuses will result in clinically relevant levels of chimerism. Appropriate animal models are needed to determine the role of HLA, cell type and quantity as well as of hematopoietic space. In fetal non-human primates immunologic and hematologic development is similar to that of the human fetus, suggesting that they should be an appropriate animal model in which to evaluate factors that may improve competitive engraftment of hematopoietic stem cells in utero.
| Shields, Laurence E; Gaur, Lakshmi; Delio, Patrick et al. (2005) The use of CD 34(+) mobilized peripheral blood as a donor cell source does not improve chimerism after in utero hematopoietic stem cell transplantation in non-human primates. J Med Primatol 34:201-8 |
| Norbeck, Oscar; Tolfvenstam, Thomas; Shields, Laurence E et al. (2004) Parvovirus B19 capsid protein VP2 inhibits hematopoiesis in vitro and in vivo: implications for therapeutic use. Exp Hematol 32:1082-7 |
| Shields, Laurence E; Gaur, Lakshmi K; Gough, Mike et al. (2003) In utero hematopoietic stem cell transplantation in nonhuman primates: the role of T cells. Stem Cells 21:304-14 |
| Shields, Laurence E; Lindton, Bim; Andrews, Robert G et al. (2002) Fetal hematopoietic stem cell transplantation: a challenge for the twenty-first century. J Hematother Stem Cell Res 11:617-31 |
