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Novel Microfluidic Approaches to Define Diabetic Progenitor Cell Dysfunction
Summary Data Summary
Applicant Gurtner, Geoffrey
E-Mail Address ggurtner@stanford.edu
Project Title Novel Microfluidic Approaches to Define Diabetic Progenitor Cell Dysfunction
CBU ID 09MCG84
External SubContract ID 23789-8
Diabetic Complication Wound Healing
Funding Program Group Pilot & Feasibility [PF2009]
Abstract Diabetes-induced impairments in new blood vessel growth greatly increase the
severity of wound healing and ischemic processes, including coronary artery
disease, cerebrovascular disease, and peripheral vascular disease. Bone marrow
(BM) derived vascular progenitor cells are believed to play a critical role in
ischemic neovascularization, and may have considerable therapeutic potential as
cell-based vectors for the repair of vascular injury. However, the specific
lineage of these cells, termed endothelial progenitor cells (EPCs), remains
unclear. Early clinical trials using BM-derived cells have yielded disappointing
and discordant results, suggesting the need for further characterization.
Mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are considered
the two most likely candidate sources, but overlap among definitions, as well as
considerable heterogeneity intrinsic to these populations, has complicated their
evaluation. We have previously demonstrated in vivo and in vitro dysfunction of
specific MSC populations using murine models of diabetes. However, overcoming
the heterogeneity inherent to such populations will ultimately require
transcriptional analysis of individual cells. To achieve this we have developed
a novel method for high-throughput single cell analysis employing microfluidic
technology. This proposal seeks to apply that technique to further characterize
HSC and MSC populations, using diabetes as a phenotypic marker of disease, to
evaluate vasculogenic potential and identify specific diabetes-induced
alterations. In Specific Aim 1, we develop a quantitative measure of population
heterogeneity and apply it to evaluate HSCs and MSCs from the BM of wild-type
(WT) and diabetic mice. A novel partitive analysis is applied in Specific Aim 2
to detect discrete MSC subpopulations and generate characteristic expression
profiles. Specific Aim 3 extends these studies to evaluate the transcriptional
response of individual subpopulations to peripheral tissue ischemia.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 13164
Supply Total Costs 15000
Equipment Total Costs 0
Travel/Other Total Costs 7981
Direct Costs 36145
Indirect Costs Proposed 23855
Total Costs Proposed 60000
Total Costs Approved 63000
Start Date 9/1/2009
End Date 8/31/2011
IFO Name Illueca, Javier
IFO E-Mail Address javieri@stanford.edu
IACUC/IRB No. A3213-01
IACUC/IRB Institution Stanford University
Entity ID No. 1941156365A1
Report Request Date 9/30/2010
T1D NO
TypeCount
Invoices 0
Progress Reports 1
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