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S. Caballero, Jr., N. Sengupta, S. LiCalzi, R.N. Mames, T. Kern, M.B. Grant; Endothelial Precursor Cells Exhibit Robust Reparative Function Of Acellular Capillaries In The Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3525.
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Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance and their function is altered in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals would be able to repopulate acellular capillaries in diabetic animals or animals that had ischemia–reperfusion (I/R) injury.
Mice were made diabetic by streptozotozin injection. At 6–9 month of diabetes, a time when acellular capillaries are present in the retina, they were injected with fluorescently–labeled CD34+ cells from nondiabetic individuals. Mice were euthanized and perfused with rhodamine–conjugated dextran 24 hrs later. In another experiment, acellular capillaries were induced by 2 hrs of hydrostatic pressure on the anterior chamber of mouse eyes in an I/R model. Seven days later fluorescently labeled CD34+ cells were injected intravitreally. One day later the animals were euthanized and handled in a manner identical to the diabetic mice. The degree of vascular repair of acellular capillaries was evaluated using confocal microscopy.
Fluorescently labeled human CD34+ cells migrated into ischemic regions of the diabetic mouse retina where vessels were obliterated and there existed acellular capillaries. CD34+ cells attached and assimilated into injured regions to reestablish blood flow in these regions. In the mice that underwent the I/R injury model, we could also demonstrate reendothelialization of acellular capillaries by EPCs.
These studies demonstrate that healthy CD34+ cells can effectively repair injured retina suggesting that in patients with diabetic retinopathy and acellular capillaries there is defective repair. Defective EPCs are amenable to pharmacological manipulation and restoration of the cells' natural robust reparative function.
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