Saturday, June 8, 2013

Stem cells for treating Diabetic Retinopathy

An article, recently published in the PLOS, refers to pericytes derived from adipose-derived (or in lay terms, fat-derived) stem cells (ASCs), being able to integrate with retinal vasculature, and providing functional vascular protection in animal models.


Pericyte
(c) Robert M Hunt
Pericytes are contractile cells that wrap around endothelial cells of capillaries and venules throughout the body. These cells regulate capillary blood flow, the clearance and phagocytosis of cellular debris, and the permeability of the blood-retinal barrier. A deficiency of pericytes can cause the barrier to break down, leading to leakage of blood and other products.

Diabetic individuals often exhibit loss of pericytes in their retina. This is a characteristic sign early on in the disease. These cells are important for the protection of endothelial cells in the retina. With their loss, microaneuryms form in the capillaries, which is the earliest clinical sign of diabetic retinopathy.

ASCs have been found to differentiate into pericytes, which suggests they may be useful as protective and regenerative cellular therapy for retinal vascular disease.

The PLOS study was undertaken by Thomas A Mendel and his colleagues, a majority of whom are from University of Virginia, Charlottesville. They found that when ASCs were injected intravitreally (inside the eye) into a murine eye subjected to oxygen-induced retinopathy (OIR) (which resembles diabetic retinopathy), the cells were capable of migrating to and integrating with the retinal vasculature. ASCs injected after OIR vessel destabilization and ablation enhanced vessel regrowth (16% reduction in avascular area). ASCs injected intravitreally before OIR vessel destabilization prevented more than 50% of retinal capillary dropout (which is commonly seen in patients with diabetic retinopathy). . Injected ASCs also prevented capillary loss in the diabetic retinopathic mouse model (79% reduction observed 2 months after injection).

The authors have concluded that ASC-derived pericytes can integrate with retinal vasculature, adopting both pericyte morphology and marker expression, and provide functional vascular protection in multiple animal models of retinal vasculopathy. The pericyte phenotype demonstrated by ASCs is enhanced with additional (TGF-β1) treatment, as seen with native retinal pericytes


The authors feel that ASCs may represent an innovative cellular therapy for protection against and repair of diabetic retinopathy and other retinal vascular diseases.



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