SEARCH:   Advanced

Blood, 15 June 2007, Vol. 109, No. 12, pp. 5178-5185. Prepublished online as a Blood First Edition Paper on March 1, 2007; DOI 10.1182/blood-2006-12-061382. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-12-061382v1 109/12/5178    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 Citing Articles via Google Scholar Google Scholar Articles by Johansson, M. K. Articles by Richter, J. Search for Related Content PubMed PubMed Citation Articles by Johansson, M. K. Articles by Richter, J. Related Collections Free Research Articles Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Hematopoietic stem cell–targeted neonatal gene therapy reverses lethally progressive osteopetrosis in oc/oc mice Maria K. Johansson1, Teun J. de Vries2, Ton Schoenmaker2, Mats Ehinger3, Ann C. M. Brun1, Anders Fasth4, Stefan Karlsson1, Vincent Everts2, and Johan Richter1 1 Department of Molecular Medicine and Gene Therapy, Lund University, Lund, Sweden; 2 Department of Periodontology and Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), Universiteit van Amsterdam and Vrije Universiteit, Amsterdam, the Netherlands; 3 Department of Pathology, Lund University, Lund, Sweden; 4 Department of Pediatrics, Göteborg University, Gothenburg, Sweden Infantile malignant osteopetrosis (IMO) is a fatal disease caused by lack of functional osteoclasts, and the only available treatment is hematopoietic stem cell (HSC) transplantation. In the majority of patients, the TCIRG1 gene, coding for a subunit of a proton pump essential for bone resorption, is mutated. Oc/oc mice have a deletion in the homologue gene (tcirg1) and die at 3 to 4 weeks, but can be rescued by neonatal transplantation of HSCs. Here, HSC-targeted gene therapy of osteopetrosis in the oc/oc mouse model was developed. Oc/oc fetal liver cells depleted of Ter119-expressing erythroid cells were transduced with a retroviral vector expressing tcirg1 and GFP, and subsequently transplanted intraperitoneally to irradiated neonatal oc/oc mice. Eight of 15 mice survived past the normal life span of oc/oc mice. In vitro osteoclastogenesis revealed formation of GFP-positive osteoclasts and bone resorption, albeit at a lower level than from wild-type cells. The skeletal phenotype was analyzed by X-ray and histopathology and showed partial correction at 8 weeks and almost normalization after 18 weeks. In summary, osteopetrosis in oc/oc mice can be reversed by neonatal transplantation of gene-modified HSCs leading to long-term survival. This represents a significant step toward the development of gene therapy for osteopetrosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Gene therapy sculpts the bone Luigi D. Notarangelo Blood 2007 109: 5067-5068. [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020