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Regenerative medicine

Endothelial progenitor cells may provide novel therapy in diabetic retinopathy

Roibeard O’hEineachain

Posted: Saturday, June 6, 2020

Regeneration of the damaged vasculature in retina from patients with diabetic retinopathy may be possible through the use of progenitor cells to restore blood flow and prevent progression to the late, sight-threatening stages of the disease, said Prof Alan Stitt PhD, Queen’s University Belfast, Northern Ireland, UK, at a meeting held in Dublin by Fighting Blindness, an Irish patient-led charity.
Prof Stitt noted that there is growing evidence that dysfunction of resident progenitor cells in vascular beds can lead to blood vessel damage and non-perfusion of diseased tissues. The normal reparative capacity of the retinal vascular endothelium is compromised in diabetes and this may, at least in part, underlie the vessel degeneration and progressive ischaemia that we see in proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DMO).
He added that detailed pre-clinical studies have shown that introducing a type of vascular progenitor cell, called endothelial colony-forming cells (ECFCS), into the ischaemic retina can regenerate blood vessels and restore perfusion thus preventing sight-threatening pathology such as proliferative retinopathy or oedema. These ECFCs can be isolated from umbilical cord blood but also from the peripheral blood of adults. The cells have many progenitor features that allow them to target areas of tissue hypoxia and participate in de novo vessel formation and integration with the existing retinal vessels, Prof Stitt said.
“These cells integrate into the resident retinal vascular endothelium and promote perfusion. They have great therapeutic potential since they can be readily isolated, expanded in the laboratory setting and, potentially, delivered to patients after appropriate tissue-typing. We have been able to achieve a significant treatment effect with as few as a thousand cells so they have quite a high level of potency and therapeutic value,” he added.
It has been noted that the introduction of new treatments for DMO, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and new forms of steroid delivery has lowered the ranking of diabetic retinopathy as a leading cause of blindness across Europe, but it still remains a very significant disease that causes vision loss. Moreover, around 40-to-50% of DMO patients do not respond optimally to the currently available therapies.
Although the evidence is only building at this point, there are some concerns that long-term anti-VEGF therapy could impact on the endogenous, homeostatic and reparative capacity of the retina and the choroid.
“It would be beneficial to develop a therapy that can promote blood vessel repair in the retina at the early and intermediate stages, before ischaemia becomes widespread and drives the late sight-threatening endpoints of DME and PDR,” Prof Stitt added.

Alan Stitt: a.stitt@qub.ac.uk


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