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Blood, 10 September 2009, Vol. 114, No. 11, pp. 2333-2343. Prepublished online as a Blood First Edition Paper on May 11, 2009; DOI 10.1182/blood-2008-10-183459. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-10-183459v1 114/11/2333    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 HighWire 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 Hematopoiesis and Stem Cells Transplantation Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation Massimo Dominici1, Valeria Rasini1, Rita Bussolari1, Xiaohua Chen2, Ted J. Hofmann2, Carlotta Spano1, Daniela Bernabei1, Elena Veronesi1, Filippo Bertoni1, Paolo Paolucci3, PierFranco Conte1, and Edwin M. Horwitz2 1 Department of Oncology and Hematology, University Hospital of Modena and Reggio Emilia, Modena, Italy; 2 Division of Oncology/Blood and Marrow Transplantation, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine; and 3 Department of Pediatrics, University Hospital of Modena and Reggio Emilia, Modena, Italy Adequate recovery of hematopoietic stem cell (HSC) niches after cytotoxic conditioning regimens is essential to successful bone marrow transplantation. Yet, very little is known about the mechanisms that drive the restoration of these niches after bone marrow injury. Here we describe a profound disruption of the marrow microenvironment after lethal total body irradiation of mice that leads to the generation of osteoblasts restoring the HSC niche, followed by a transient, reversible expansion of this niche. Within 48 hours after irradiation, surviving host megakaryocytes were observed close to the endosteal surface of trabecular bone rather than in their normal parasinusoidal site concomitant with an increased stromal-derived factor-1 level. A subsequent increase in 2 megakaryocyte-derived growth factors, platelet-derived growth factor-β and basic fibroblast growth factor, induces a 2-fold expansion of the population of N-cadherin-/osteopontin-positive osteoblasts, relative to the homeostatic osteoblast population, and hence, increases the number of potential niches for HSC engraftment. After donor cell engraftment, this expanded microenvironment reverts to its homeostatic state. Our results demonstrate the rapid recovery of osteoblastic stem cell niches after marrow radioablation, provide critical insights into the associated mechanisms, and suggest novel means to manipulate the bone marrow microenvironment to promote HSC engraftment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The osteoblastic niche following TBI Susie Nilsson Blood 2009 114: 2210-2211. [Full Text] [PDF] This article has been cited by other articles: S. Nilsson The osteoblastic niche following TBI Blood, September 10, 2009; 114(11): 2210 - 2211. [Full Text] [PDF]

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