Regenerative Therapeutic Potential of Adipose Stromal Cells in Early Stage Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved “b” wave amplitude (as measured by electroretinogram) within 1–3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration.

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

“…MSCs could thus have a great impact on DR treatment since they can act as immunomodulatory agents and reactive oxygen species (ROS) scavengers [98]. Furthermore, due to striking similarities between MSCs and pericytes, MSCs might replace the latter, thereby compensating for pericyte loss [99]; Mendel et al, and Rajashekhar et al, have shown that adipose-derived MSCs intravitreally injected into diabetic mice were able to migrate and integrate into the retinal vasculature, leading to microvascular stabilisation and a marked reduction in capillary dropout [100,101].…”

The potential of mesenchymal stem cells in diabetes mellitus

“…This study demonstrated that the adipose-derived stromal cells can rescue the neural retina from hyperglycemia-induced degeneration, and improved visual function. 19 …”

Stem cell therapies in the treatment of diabetic retinopathy and keratopathy

“…113 Moreover, ASCs intravitreal inoculation into type I diabetic athymic nude rat led to improvement of electroretinogram, thus also providing neuroprotection. 114 Pluripotent stem cells (PSC) represented until recent discovery of induced PSC (iPSC) mostly by embryonic stem cells (ESC) are able to differentiate into any cell type of all three main lineages. ESC-derived retinal progenitor cells showed their ability to integrate and differentiate into functional photoreceptors, as evidenced by a significant improvement of vision in mouse models of retinal degeneration, 115,116 although it is unclear whether neuroretinal replacement is likely to be successful in diabetes.…”