Human Umbilical Cord Blood-Derived CD133+CD34+ Cells Protect Retinal Endothelial Cells and Ganglion Cells in X-Irradiated Rats through Angioprotective and Neurotrophic Factors

Abstract

Radiation retinopathy (RR) is a common complication following radiation therapy of globe, head, and neck malignancies, and is characterized by microangiopathy, neuroretinopathy, and the irreversible loss of visual function. To date, there is no effective treatment for RR. Stem cells have been clinically used to treat retinal degeneration. CD133+CD34+ cells from human umbilical cord blood (hUCB-CD133+CD34+ cells), a subpopulation of hematopoietic stem cells, were applied to determine their protective efficacy on irradiated rat retinas. After X-ray irradiation on the retinas, rats were intravitreally injected with hUCB-CD133+CD34+ cells. Transplantation of hUCB-CD133+CD34+ cells prevented retinal dysfunction 2 weeks post-operation and lasted at least 8 weeks. CD133+CD34+ cells were distributed along the retinal vessel and migrated to the ganglion cell layer. Moreover, grafted CD133+CD34+ cells reduced the apoptosis of endothelial and ganglion cells in irradiated rats and increased the number of survived CD31+ retinal endothelial cells and Brn3a+ ganglion cells at 2 and 4 weeks, respectively, post-operation. Co-culturing of CD133+CD34+ cells or supernatants with irradiated human retinal microvascular endothelial cells (hRECs) in vitro, confirmed that CD133+CD34+ cells ameliorated hREC apoptosis caused by irradiation. Mechanistically, we found that angioprotective mediators and neurotrophic factors were secreted by CD133+CD34+ cells, which might attenuate irradiation-induced injury of retinal endothelial cells and ganglion cells. hUCB-CD133+CD34+ cell transplantation, as a novel treatment, protects retinal endothelial and ganglion cells of X-irradiated rat retinas, possibly through angioprotective and neurotrophic factors.

The association between circulating CD34+CD133+ endothelial progenitor cells and reduced risk of Alzheimer’s disease in the Framingham Heart Study

“…Our longitudinal cohort found that circulating CD34+CD133+ EPCs were negatively associated with AD risk, suggesting a protective role against AD risk via repairing damaged endothelia in cerebrovasculature. Consistently with our finding, circulating EPCs with the co-expression of CD34, CD133, and KDR have pronounced tube formation activity in vitro, and strong reendothelialization or neovascularization capacity in vivo [36].…”

Circulating Endothelial Progenitor Cells Reduce the Risk of Alzheimer’s Disease

“…10 Human cord blood CD133+CD34+ cells have been shown to reduce the apoptosis of endothelial and ganglion cells and increase the number of surviving CD31+ mature endothelial cells in the retina after radiation damage. 17 CD34 (also known as sialomucin) is a transmembrane protein expressed on early hematopoietic and vascular-associated tissues. 18 CD133 is a stem cell marker, and peripheral blood-derived CD133+ cells can further differentiate into hematopoietic, endothelial, and muscle cells in vivo and in vitro .…”