The proposed studies will use innovative approaches to expand the use of iPS to change treatment paradigms for NIDDK-related diseases. We therefore hypothesize that murine iPS cell derived mesenchymal stem cells and adipocytes offer the potential for cell-based therapy to treat lipodystrophy. We propose to create a set of mouse iPS cell models of lipodystrophy using transgene-free approaches for the purpose of evaluating the differentiation potential of young versus aged derived iPS relative to BM-MSC to mesenchymal and adipose lineages and subsequent function. We will also test the ability of the iPS cell derived mesenchymal stem cells to rescue a mouse model of lipodystrophy relative to BM-MSC. This model will enable us to identify a cell type which may be suited as a potential therapy. Additionally, these studies will generate important resources and reagents that will be of vast interest to both the scientific and medical communities.

Public Health Relevance

Lipodystrophies are the result of adipose tissue degeneration as well as misdistribution and result in severe defects in lipid and glucose homeostasis. The therapeutic potential of iPS derived mesenchymal stem cells for tissue repair and regeneration is almost limitless with respect to lipodystrophy. These studies will enable the delivery of truly personalized medical treatment for lipodystrophy since the iPS cells would be eventually generated from the same individual in need of treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DK094132-02
Application #
8542832
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2012-09-15
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$188,175
Indirect Cost
$67,550
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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West, James D; Austin, Eric D; Gaskill, Christa et al. (2014) Identification of a common Wnt-associated genetic signature across multiple cell types in pulmonary arterial hypertension. Am J Physiol Cell Physiol 307:C415-30