Therapeutic potential of human neural precursor cells in diabetic retinopathy—preclinical model

Abstract

Background Considering the expressive number of individuals being diagnosed with diabetes worldwide, it is relevant to find medicines and treatments, in order to achieve diabetes complications, as diabetic retinopathy (DR) long-awaited regression and/or cure. The study aimed to evaluate cell therapy with human neural precursor cells (hNPCs) on induced diabetic retinopathy (DR) in Wistar rats. Methods Wharton's Jelly Mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate without growth factors to develop neurospheres, then hNPCs were obtained and characterized by immunocytochemistry. The animals were divided into three groups; non-diabetic (ND) n = 4; diabetic without treatment (DM) n = 9; diabetic with cell therapy (DM + hNPCs) n = 9. Cells were transplanted by intravitreal injection (1 x 106 cel/µL) into each of Streptozotocin (STZ) induced diabetes rats. Evaluations by Optical Coherence Tomography (OCT) and Electroretinography (ERG) were done before and after diabetes induction and post cell therapy. Four weeks after treatment, eye enucleation allowed histopathological and immunohistochemistry (IHC) analysis. Results hNPCs increased the number of retina ganglion cells, ameliorated the photoreceptor layer, and decreased the microvessel points, evidenced by ERG, OCT, histopathological, and IHC findings. The most relevant differences in morphological analysis (treated vs untreated), exhibit the retinal improvement in many layers, notably in the retinal pigment epithelium and photoreceptors. Conclusions hNPCs reduced DR progression, as demonstrated by a neuroprotective effect and promotion of retinal regeneration.