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In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta.
- Source :
-
Blood [Blood] 2009 Jul 09; Vol. 114 (2), pp. 459-68. Date of Electronic Publication: 2009 May 04. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Bone Marrow Cells cytology
Collagen metabolism
Disease Models, Animal
Extracellular Space chemistry
Female
Gene Knock-In Techniques
Genes, Dominant
Graft Survival
Mice
Mice, Transgenic
Osteogenesis Imperfecta metabolism
Osteogenesis Imperfecta pathology
Phenotype
Pregnancy
Spectrum Analysis, Raman
Survival Rate
Tissue Donors
Aging physiology
Bone Marrow Transplantation methods
Fetal Research
Osteogenesis Imperfecta prevention & control
Osteogenesis Imperfecta therapy
Uterus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 114
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 19414862
- Full Text :
- https://doi.org/10.1182/blood-2008-12-195859