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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4386-4391. Prepublished online as a Blood First Edition Paper on January 8, 2008; DOI 10.1182/blood-2007-10-115725. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-10-115725v1 111/8/4386    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Google Scholar Articles by Dominici, M. Articles by Horwitz, E. M. PubMed PubMed Citation Articles by Dominici, M. Articles by Horwitz, E. M. Related Collections Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Donor cell–derived osteopoiesis originates from a self-renewing stem cell with a limited regenerative contribution after transplantation Massimo Dominici1, Roberta Marino2,3, Valeria Rasini1, Carlotta Spano1, Paolo Paolucci4, Pierfranco Conte1, Ted J. Hofmann2,5, and Edwin M. Horwitz2,5 1 Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy; 2 Division of Bone Marrow Transplantation, St Jude Children's Research Hospital, Memphis, TN; 3 Department of Pediatrics, Federal University of Sao Paulo, Sao Paulo, Brazil; 4 Department of Pediatrics, University of Modena and Reggio Emilia, Modena, Italy; 5 Division of Oncology/Blood and Marrow Transplantation, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia In principle, bone marrow transplantation should offer effective treatment for disorders originating from defects in mesenchymal stem cells. Results with the bone disease osteogenesis imperfecta support this hypothesis, although the rate of clinical improvement seen early after transplantation does not persist long term, raising questions as to the regenerative capacity of the donor-derived mesenchymal progenitors. We therefore studied the kinetics and histologic/anatomic pattern of osteopoietic engraftment after transplantation of GFP-expressing nonadherent marrow cells in mice. Serial tracking of donor-derived GFP+ cells over 52 weeks showed abundant clusters of donor-derived osteoblasts/osteocytes in the epiphysis and metaphysis but not the diaphysis, a distribution that paralleled the sites of initial hematopoietic engraftment. Osteopoietic chimerism decreased from approximately 30% to 10% by 24 weeks after transplantation, declining to negligible levels thereafter. Secondary transplantation studies provided evidence for a self-renewing osteopoietic stem cell in the marrow graft. We conclude that a transplantable, primitive, self-renewing osteopoietic cell within the nonadherent marrow cell population engrafts in an endosteal niche, like hematopoietic stem cells, and regenerates a significant fraction of all bone cells. The lack of durable donor-derived osteopoiesis may reflect an intrinsic genetic program or exogenous environmental signaling that suppresses the differentiation capacity of the donor stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Osteopoietic stem cells: transplantable, but regeneratively limited Susie Nilsson Blood 2008 111: 3917-3918. [Full Text] [PDF]

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