March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Adult Endothelial Progenitor Cell Populations: Functional Differences in Diabetic Retinopathy
Author Affiliations & Notes
  • Sergio Caballero, Jr.
    Pharmacology/Therapeutics, University of Florida, Gainesville, Florida
  • Sugata Hazra
    Pharmacology/Therapeutics, University of Florida, Gainesville, Florida
  • Ashay Bhatwadekar
    Pharmacology/Therapeutics, University of Florida, Gainesville, Florida
  • Sergio Li Calzi
    Pharmacology/Therapeutics, University of Florida, Gainesville, Florida
  • Linda J. Paradisio
    America Stem Cell, Inc., Helotes, Texas
  • Len Miller
    America Stem Cell, Inc., Helotes, Texas
  • Timothy S. Kern
    Department of Medicine, Case Western Reserve University, Cleveland, Ohio
  • Maria B. Grant
    Pharmacology/Therapeutics, University of Florida, Gainesville, Florida
  • Footnotes
    Commercial Relationships  Sergio Caballero, Jr., None; Sugata Hazra, None; Ashay Bhatwadekar, None; Sergio Li Calzi, None; Linda J. Paradisio, America Stem Cell, Inc. (E, P); Len Miller, America Stem Cell, Inc. (E, P); Timothy S. Kern, None; Maria B. Grant, Research materials (F)
  • Footnotes
    Support  NIH Grants EY007739, EY012601, HL087366, DK090730 to MBG
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5781. doi:
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      Sergio Caballero, Jr., Sugata Hazra, Ashay Bhatwadekar, Sergio Li Calzi, Linda J. Paradisio, Len Miller, Timothy S. Kern, Maria B. Grant; Adult Endothelial Progenitor Cell Populations: Functional Differences in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5781.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : CD34+ EPCs function aberrantly in diabetes & cannot repair damaged retinal vessels. CD14+ EPCs become monocytes but can exhibit functional & phenotypic endothelial cell characteristics under certain conditions. We examined the homing of these cells & the effect of ex vivo manipulation on their homing ability to injured retinal vessels, using streptozotocin (STZ)-diabetes & ischemia/reperfusion injury models in mice.

Methods: : STZ mice of either ≤ 4 mo or ≥ 10 mo diabetes duration, & age- & gender-matched controls, were given 105 huCD34+ or CD14+ cells from healthy or diabetic donors intravitreously. EPCs were differentially prelabeled with fluorescent nanoparticles, & their location was examined by immunofluorescent confocal microscopy (IFCM) after 2 days. Separately, huCD34+ EPCs from diabetic donors were treated with a proprietary reagent (ASC 101) that adds fucose to cell surface glycoproteins (fucosylation) to enhance selectin-mediated binding to endothelial luminal surface. These cells were given to mice with ocular ischemia/reperfusion injury & location determined by IFCM.

Results: : Diabetic CD34+ EPCs show some vessl association in early diabetes but significantly less than healthy CD34+ cells. This decreases late in disease until nearly all diabetic CD34+ cells have a clumped & random distribution. Age alone increases retinal vessel damage seen by increased vascular homing of healthy CD34+ EPCs in aged mice. Diabetes results in more homing of healthy EPCs to vessels than age alone. While diabetic CD34+ EPCs show poor vascular association, diabetic CD14+ EPCs associate with diabetic vasculature more than even healthy CD14+ EPCs, nearly the same degree as healthy cells. Fucosylation of diabetic CD34+ EPCs greatly improves homing and association with injured vessels, resulting in a 2.5 +/- 0.6 fold increase (p=0.05) in fucosylated cells colocalized with vessels vs. untreated cells.

Conclusions: : In healthy individuals CD34+ EPCs home to & associate with damaged vasculature, presumably to cause repair. However, in diabetes this population loses that ability and the CD14+ EPCs predominate. Since these cells usually result in inflammatory monocytes, their predominance in diabetic vessels may increase pathology. Ex vivo fucosylation of diabetic CD34+ EPCs restores their ability to home to & associate with diabetic retinal vasculature. While it may be possible to correct functional defects of diabetic EPCs, cellular therapies for diabetic retinopathy must account for the differential behavior of EPC subpopulations. These findings hold promise for autologous stem and progenitor cell therapy for diabetic retinopathy.

Keywords: retinal neovascularization • diabetic retinopathy • diabetes 

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