Ischemic Vascular Damage Can Be Repaired by Healthy, but Not Diabetic, Endothelial Progenitor Cells

TLDR

EPCs are essential for vascular repair, yet their function is impaired in diabetes, suggesting that restoring EPC activity could be therapeutically beneficial. The study examined whether healthy human EPCs can repopulate acellular retinal capillaries in diabetic and ischemic injury models compared to diabetic EPCs. Fluorescently labeled CD34⁺ cells from healthy or diabetic donors were injected into diabetic mice, diabetic rats, I/R‑injured mice, or OIR mice, and vascular repair was assessed histologically over time. Healthy EPCs successfully integrated into damaged retinal vessels in all four models, whereas diabetic EPCs failed to repair vasculature, confirming defective repair in diabetic patients.

Abstract

Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded 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 are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage. Streptozotocin-induced diabetic mice, spontaneously diabetic BBZDR/Wor rats, adult mice with I/R injury, or neonatal mice with OIR were injected within the vitreous or the systemic circulation with fluorescently labeled CD34(+) cells from either diabetic patients or age- and sex-matched healthy control subjects. At specific times after administering the cells, the degree of vascular repair of the acellular capillaries was evaluated immunohistologically and quantitated. In all four models, healthy human (hu)CD34(+) cells attached and assimilated into vasculature, whereas cells from diabetic donors uniformly were unable to integrate into damaged vasculature. These studies demonstrate that healthy huCD34(+) cells can effectively repair injured retina and that there is defective repair of vasculature in patients with diabetes. Defective EPCs may be amenable to pharmacological manipulation and restoration of the cells' natural robust reparative function.