Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Type: Journal article
Title: In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, cominant osteogenesis imperfecta
Author: Panaroni, C.
Gioia, R.
Lupi, A.
Besio, R.
Goldstein, S.
Kreider, J.
Leikin, S.
Vera, J.
Mertz, E.
Perilli, E.
Baruffaldi, F.
Villa, I.
Farina, A.
Casasco, M.
Cetta, G.
Rossi, A.
Frattini, A.
Marini, J.
Vezzoni, P.
Forlino, A.
Citation: Blood, 2009; 114(2):459-468
Publisher: Amer Soc Hematology
Issue Date: 2009
ISSN: 0006-4971
Statement of
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
Abstract: 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 (IUT) 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 knockin mouse with a classical glycine substitution in type I collagen [alpha1(I)-Gly349Cys], dominant trait transmission, and a phenotype resembling moderately severe and lethal OI. Adult bone marrow donor cells from enhanced green fluorescent protein (eGFP) transgenic mice engrafted in hematopoietic and nonhematopoietic 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 < .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 IUT as a promising approach for the treatment of genetic bone diseases.
Keywords: Uterus
Bone Marrow Cells
Extracellular Space
Mice, Transgenic
Osteogenesis Imperfecta
Disease Models, Animal
Bone Marrow Transplantation
Spectrum Analysis, Raman
Survival Rate
Fetal Research
Graft Survival
Genes, Dominant
Tissue Donors
Gene Knock-In Techniques
Description: Copyright © 2009 by American Society of Hematology
DOI: 10.1182/blood-2008-12-195859
Published version:
Appears in Collections:Aurora harvest 5
Pathology publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.