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

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, Antonella Forlino

Research output: Contribution to journalArticlepeer-review

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 [α1(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.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalBlood
Volume114
Issue number2
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this