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Blood, 9 July 2009, Vol. 114, No. 2, pp. 459-468. Prepublished online as a Blood First Edition Paper on May 4, 2009; DOI 10.1182/blood-2008-12-195859. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-12-195859v1 114/2/459    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 Panaroni, C. Articles by Forlino, A. Search for Related Content PubMed PubMed Citation Articles by Panaroni, C. Articles by Forlino, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 22, 2008 Accepted April 27, 2009 In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knock-in murine model for classical, dominant osteogenesis imperfecta Cristina Panaroni, Roberta Gioia, Anna Lupi, Roberta Besio, Steven A. Goldstein, Jaclynn Kreider, Sergey Leikin, Juan Carlos Vera, Edward L. Mertz, Egon Perilli, Fabio Baruffaldi, Isabella Villa, Aurora Farina, Marco Casasco, Giuseppe Cetta, Antonio Rossi, Annalisa Frattini, Joan C. Marini, Paolo Vezzoni, and Antonella Forlino* ITB-CNR, Milan, Italy Department of Biochemistry, University of Pavia, Pavia, Italy Orthopaedic Research Laboratories, University of Michigan, Ann Arbor, MI, United States Section on Physical Biochemistry, NICHD, NIH, Bethesda, MD, United States Laboratorio di Tecnologia Medica, Istituti Ortopedici Rizzoli, Bologna, Italy Bone Metabolic Unit San Raffaele Scientific Institute, Milan, Italy Department of Experimental Medicine, Section of Histology and Embryology, University of Pavia, Pavia, Italy Istituto Clinico Humanitas, Rozzano, Italy Section on Connective Tissue Disorders, BEMB, NICHD, NIH, Bethesda, MD, United States * Corresponding author; email: aforlino{at}unipv.it. Autosomal dominant osteogenesis imperfecta (OI) caused by glycine substitutions in type I collagen is a paradigmatic disorder for stem cell therapy. Bone marrow transplantation in OI children has produced a low engraftment rate, but surprisingly encouraging symptomatic improvements. In utero transplantation may hold even more promise. However, systematic studies of both methods have so far been limited to a recessive mouse model. In this study, we evaluated intrauterine transplantation of adult bone marrow into heterozygous BrtlIV mice. Brtl is a knock-in mouse with a classical glycine substitution in type I collagen (1(I)-Gly349Cys), dominant trait transmission, and a phenotype resembling moderately severe and lethal OI. Adult bone marrow donor cells from eGFP transgenic mice engrafted in haematopoietic and non haematopoietic tissues, differentiated to trabecular and cortical bone cells, and synthesized up to 20% of all type I collagen in the host bone. The transplantation eliminated the perinatal lethality of heterozygous BrtlIV mice. At 2 months of age, femora of treated Brtl mice had significant improvement in geometric parameters (p<0.05) versus untreated Brtl mice, and their mechanical properties attained wild-type values. Our results suggest that the engrafted cells form bone with higher efficiency than the endogenous cells, supporting in utero transplantation as a promising approach for the treatment of genetic bone diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. H. Undale, J. J. Westendorf, M. J. Yaszemski, and S. Khosla Mesenchymal Stem Cells for Bone Repair and Metabolic Bone Diseases Mayo Clin. Proc., October 1, 2009; 84(10): 893 - 902. [Abstract] [Full Text] [PDF]

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