Human Dental Pulp Stem Cells (DPSCs) Therapy in Rescuing Photoreceptors and Establishing a Sodium Iodate-Induced Retinal Degeneration Rat Model

Abstract

Background: Different methods have been used to inject stem cells into the eye for research. We previously explored the intravitreal route. Here, we investigate the efficacy of intravenous and subretinal-transplanted human dental pulp stem cells (DPSCs) in rescuing the photoreceptors of a sodium iodate-induced retinal degeneration model. Methods: Three groups of Sprague Dawley rats were used: intervention, vehicle group and negative control groups (n = 6 in each). Intravenous injection of 60 mg/kg sodium iodate (day 0) induced retinal degeneration. On day 4 post-injection of sodium iodate, the rats in the intervention group received intravenous DPSC and subretinal DPSC in the right eye; rats in the vehicle group received subretinal Hank's balance salt solution and intravenous normal saline; while negative control group received nothing. Electroretinogram (ERG) was performed to assess the retinal function at day 0 (baseline), day 4, day 11, day 18, day 26, and day 32. By the end of the study at day 32, the rats were euthanized, and both their enucleated eyes were sent for histology. Results: No significant difference in maximal ERG a-wave (p = 0.107) and bwave, (p = 0.153) amplitude was seen amongst the experimental groups. However, photopic 30 Hz flicker amplitude of the study eye showed significant differences in the 3 groups (p = 0.032). Within the intervention group, there was an improvement in 30 Hz flicker ERG response of all 6 treated right eyes, which was injected with subretinal DPSC; while the 30 Hz flicker ERG of the non-treated left eyes remained flat. Histology showed improved outer nuclear layer thickness in intervention group; however, findings were not significant compared to the negative and vehicle groups. Conclusion: Combination of subretinal and intravenous injection of DPSCs may have potential to rescue cone function from a NaIO3induced retinal injury model.

A concise review of the orofacial mesenchymal stromal cells as a novel therapy for neurological diseases and injuries

“…In addition, transplantation of PDLSCs could promote RGCs survival and axonal regeneration after optic nerve injury through secretion of neurotrophic factors such as BDNF (Cen et al, 2018). Recently, subretinal and intravenous transplantation of DPSCs also showed therapeutic efficacy for a sodium iodate-induced retinal degeneration rat model, which was confirmed by the electroretinogram response (Lam et al, 2021). The underlying mechanism of the therapeutic potential of DPSCs may be related to their ability to respond to cues from the rat retina and differentiate into retinal ganglion-like cells (Bray et al, 2014;Roozafzoon et al, 2015).…”

Rescue of photoreceptor with human mesenchyme stem cell and human mesenchyme stem cell expressing erythropoietin in total degeneration of retina animal model

“…Subsequently, on day 18, a booster of intravenous injection of HDUMSC, HDUMSC-EPO, and HBSS was given respectively to the HDUMSC, HDUMSC-EPO, and HBSS groups as it is found that the effect of MSC declines by day 10 post injection. [ 29 30 ] The rats were then anesthetized with 150 mg/kg ketamine (Bioketan, Vetoquinol Biowet, Poland) and 10 mg/kg xylazine (Xylazil-20 Troy Lab Australia) before a transscleral cut was performed for subretinal injection with a 30G needle. A total of 3 μL (1 × 10 5 cell count) of HDUMSC or HDUMSC-EPO cells were carefully injected subretinally with a Hamilton syringe (internal diameter: 75–150 μm) to avoid retinal detachment.…”

Therapeutic potential of dental pulp stem cells and their derivatives: Insights from basic research toward clinical applications

“…These mediators have no therapeutic effect and only serve as transport vectors for stem cells, so it is possible to observe the monotherapy effect of transplanted stem cells and rule out the influence of carriers. In addition, DPSC injections are usually administered by local injection[ 15 , 66 , 69 , 80 ], intramuscular injection[ 67 , 76 , 81 ] and intravenous injection[ 67 , 68 , 72 , 82 ]. Different methods of administration lead to different systemic distributions and different efficacies.…”

“…This result indicated a differential distribution pattern of transplanted DPSCs between the intravenous and local injections. Both intravenously and locally injected DPSCs have been shown to improve symptoms of various lesions[ 15 , 72 , 76 , 80 ]. DPSCs have also been shown to migrate and integrate into the site of injuries[ 15 , 69 , 73 , 74 ] and differentiate into corresponding cells[ 68 , 72 , 75 , 79 , 84 ].…”