Induction of Differentiation of Mesenchymal Stem Cells into Retinal Pigment Epithelial Cells for Retinal Regeneration by Using Ciliary Neurotrophic Factor in Diabetic Rats.

Abstract

Diabetic retinopathy (DR) is a common cause of blindness all over the world. Bone marrow mesenchymal stem cells (BMSCs) have been considered as a promising strategy for retinal regeneration in the treatment of DR. However, the poor viability and low levels of BMSCs engraftment limit the therapeutic potential of BMSCs. The present study aimed to examine the direct induction of BMSCs differentiation into the cell types related to retinal regeneration by using soluble cytokine ciliary neurotrophic factor (CNTF). We observed remarkably increased expression of cellular retinaldehyde-binding protein (CRALBP) and retinoid isomerohydrolase (RPE65) in BMSCs treated with CNTF in vitro, indicating the directional differentiation of BMSCs into the retinal pigment epithelium (RPE) cells, which are crucial for retinal healing. In vivo, the diabetic rat model was established by use of streptozotocin (STZ), and animals treated with BMSCs+CNTF exhibited better viability and higher delivery efficiency of the transplanted cells than those treated with BMSCs injection alone. Similar to the in-vitro result, treatment with BMSCs and CNTF combined led to the differentiation of BMSCs into beneficial cells (RPE cells), and accelerated retinal healing characterized by the activation of rod photoreceptor cells and phagocytosis function of RPE cells. In conclusion, CNTF contributes to the differentiation of BMSCs into RPE cells, which may help overcome the current stem cell therapy limitations in the field of retinal regeneration.