Osteogenesis Imperfecta (OI) that has an incidence of 1/10,000 - 1/20,000 live births, has frequently served as a model disorder for dominant negative conditions of structural proteins. Effective therapy for these disorders will require direct or targeted replacement of a mutated gene with wild-type allele. This research proposal will explore the possibility that patients with OI can potentially be treated with their own osteoprogenitors by gene-engineering the cells from their bone marrow that are referred to as mesenchymal stem cells or marrow stromal cells (MSCs). The marrow stromal cells will be used to test the hypothesis that marrow stromal cells from the patients with OI can be gene-engineered to correct the deleterious effects of mutations in type I collagen that produce the disease.
The Specific Aims for this proposal are: (1) To obtain homologous recombination of the COL1A1 gene in human MSCs to determine the possibility of alleviating the OI symptoms by replacing the mutant allele with wild type allele of COL1A1 (2) To obtain over-expression clones of hMSCs that express COL1A1 cDNA to determine the effect of ratio of wild-type to mutant COL1A1 protein (3) To study the repair potential and homing of gene engineered hMSCs; the repair potential of gene engineered MSCs will be determined by injecting the cells into the fracture model and control mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR048481-03
Application #
6800150
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Sharrock, William J
Project Start
2002-08-05
Project End
2005-01-01
Budget Start
2004-08-05
Budget End
2005-01-01
Support Year
3
Fiscal Year
2004
Total Cost
$20,352
Indirect Cost
Name
Tulane University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Penfornis, Patrice; Pochampally, Radhika (2011) Isolation and expansion of mesenchymal stem cells/multipotential stromal cells from human bone marrow. Methods Mol Biol 698:11-21
DeComas, Amalia M; Penfornis, Patrice; Harris, Michael R et al. (2010) Derivation and characterization of an extra-axial chordoma cell line (EACH-1) from a scapular tumor. J Bone Joint Surg Am 92:1231-40