The overall aim of this proposal is to answer two related questions about marrow stromal cells (MSCs): (1) do MSCs normally serve as a continuing source of precursor cells for renewal of many of the mesenchymal tissues of the body?; and (2) will further experiments in transgenic mice support preliminary observations, suggesting that systemic administration of MSCs can be used for cell replacement therapy and ex vivo gene therapy of osteogenesis imperfecta, and perhaps several other genetic diseases? The experimental protocols used to attempt to answer these two questions will be designed so that, if they produce positive results in transgenic mice, they can be subsequently used to design protocols for testing similar therapies, first in larger animals, and then in patients with osteogenesis imperfecta (OI) and related genetic diseases.
The Specific Aims are: (1) to further define the tissue fate of MSCs that are infused systemically into mice, by preparing MSCs expressing marker genes driven by tissue-specific promoters, and infusing these cells into irradiated and non-irradiated mice; and (2) to determine the degree to which the OI phenotype can be rescued in transgenic mice expressing a mutated COL1A1 gene, by administration of MSCs from normal mice, and MSCs over-expressing a normal COL1A1 allele.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
7R01AR044210-06
Application #
6361392
Study Section
Special Emphasis Panel (ZRG4-ORTH (05))
Program Officer
Sharrock, William J
Project Start
1997-04-18
Project End
2002-03-31
Budget Start
2000-07-01
Budget End
2002-03-31
Support Year
6
Fiscal Year
2000
Total Cost
$223,511
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
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Sekiya, Ichiro; Larson, Benjamin L; Smith, Jason R et al. (2002) Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells 20:530-41
Tremain, N; Korkko, J; Ibberson, D et al. (2001) MicroSAGE analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages. Stem Cells 19:408-18
Schwarz, E J; Reger, R L; Alexander, G M et al. (2001) Rat marrow stromal cells rapidly transduced with a self-inactivating retrovirus synthesize L-DOPA in vitro. Gene Ther 8:1214-23
Sekiya, I; Colter, D C; Prockop, D J (2001) BMP-6 enhances chondrogenesis in a subpopulation of human marrow stromal cells. Biochem Biophys Res Commun 284:411-8

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