Geoffrey Gurtner

Personal Information
Title Professor
Expertise Wound Healing
Institution Stanford University
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Data Summary
Grants/SubContracts 2
Progress Reports 2
Presentations 1
Publications 10
Protocols 0
Committees 3

The Role of Oxidative Stress in Diabetes Induced Progenitor Cell Deficits
Diabetes affects 25.8 million people in the United States (8.3% of the population), and is particularly detrimental to the vascular system. Our laboratory has delineated specific and discrete defects in a number of stem/progenitor cell populations in diabetes that may underlie impaired wound healing and neovascularization. We have also recently identified the enzyme glyoxalase 1 (Glo1) (a regulator of glycolysis-derived methylgloxal [MG] formation and production of reactive oxygen species [ROS]) as a critical regulator of diabetic vascular and end organ dysfunction. In this proposal, we build on these novel findings to test our fundamental hypothesis that diabetic progenitor cell defects are the result of MG-induced oxidative stress, and that normalization of this stress through modulation of the MG-regulating enzyme Glo1 will prevent and reverse diabetic progenitor cell defects and wound healing sequelae. This work will determine whether restoration of progenitor defects by reducing MG-derived ROS is a clinically viable strategy to treat diabetic complications.
Novel Microfluidic Approaches to Define Diabetic Progenitor Cell Dysfunction
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.

Progress Reports

Annual Reports
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 PublicationAltmetricsSubmitted ByPubMed IDStatus

Year: 2015; Items: 1

Progenitor Cell Dysfunctions Underlie Some Diabetic Complications.
Rodrigues M, Wong VW, Rennert RC, Davis CR, Longaker MT, Gurtner GC
The American journal of pathology, 2015

Year: 2014; Items: 1

Diabetes Irreversibly Depletes Bone Marrow-Derived Mesenchymal Progenitor Cell Subpopulations.
Januszyk M, Sorkin M, Glotzbach JP, Vial IN, Maan Z, Rennert RC, Duscher D, Thangarajah H, Longaker MT, Butte AJ, Gurtner GC
Diabetes, 2014 (63), 3047 - 3056

Year: 2011; Items: 1

Antimycotic ciclopirox olamine in the diabetic environment promotes angiogenesis and enhances wound healing.
Ko SH, Nauta A, Morrison SD, Zhou H, Zimmermann A, Gurtner GC, Ding S, Longaker MT
PLoS ONE, 2011 (6), e27844
Submitted Externally

Year: 2010; Items: 1

HIF-1alpha dysfunction in diabetes.
Thangarajah H, Vial IN, Grogan RH, Yao D, Shi Y, Januszyk M, Galiano RD, Chang EI, Galvez MG, Glotzbach JP, Wong VW, Brownlee M, Gurtner GC
Cell cycle (Georgetown, Tex.), 2010 (9), 75 - 79

Year: 2009; Items: 6

IFATS collection: Adipose stromal cells adopt a proangiogenic phenotype under the influence of hypoxia.
Thangarajah H, Vial IN, Chang E, El-Ftesi S, Januszyk M, Chang EI, Paterno J, Neofytou E, Longaker MT, Gurtner GC
Stem Cells, 2009 (27), 266 - 274
Tissue engineering using autologous microcirculatory beds as vascularized bioscaffolds.
Chang EI, Bonillas RG, El-ftesi S, Chang EI, Ceradini DJ, Vial IN, Chan DA, Michaels J, Gurtner GC
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009 (23), 906 - 915
Topical lineage-negative progenitor-cell therapy for diabetic wounds (invited discussion).
Gurtner GC, Longaker MT
Plastic and reconstructive surgery, 2009 (123), 421 - 423
Submitted Externally
Aging and diabetes impair the neovascular potential of adipose-derived stromal cells.
El-Ftesi S, Chang EI, Longaker MT, Gurtner GC
Plastic and reconstructive surgery, 2009 (123), 475 - 485
Mesenchymal stem cells can participate in ischemic neovascularization.
Hamou C, Callaghan MJ, Thangarajah H, Chang E, Chang EI, Grogan RH, Paterno J, Vial IN, Jazayeri L, Gurtner GC
Plastic and reconstructive surgery, 2009 (123), 45S - 55S
The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues.
Thangarajah H, Yao D, Chang EI, Shi Y, Jazayeri L, Vial IN, Galiano RD, Du XL, Grogan R, Galvez MG, Januszyk M, Brownlee M, Gurtner GC
Proceedings of the National Academy of Sciences of the United States of America, 2009 (106), 13505 - 13510
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Title YearTypeOptions
Gurtner, Geoffrey (2009 P&F)
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