人牙髓干细胞（DPSCs）治疗在挽救光感受器和建立碘酸钠诱导的视网膜变性大鼠模型中的应用。
Human Dental Pulp Stem Cells (DPSCs) Therapy in Rescuing Photoreceptors and Establishing a Sodium Iodate-Induced Retinal Degeneration Rat Model.
机构信息
Faculty of Medicine, Department of Ophthalmology, UKM Medical Centre, 56000, Cheras, Kuala Lumpur, Malaysia.
Department of Medical Microbiology and Parasitology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
出版信息
Tissue Eng Regen Med. 2021 Feb;18(1):143-154. doi: 10.1007/s13770-020-00312-1. Epub 2021 Jan 7.
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 b-wave, (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 NaIO-induced retinal injury model.
背景
为了进行研究，人们已经尝试了多种向眼部注射干细胞的方法。我们之前探索过玻璃体内注射途径，本研究旨在探讨静脉内和视网膜下移植人牙髓干细胞（DPSCs）在挽救碘酸钠诱导的视网膜变性模型中的光感受器方面的疗效。
方法
使用三组 Sprague Dawley 大鼠：干预组、载体组和阴性对照组（每组 6 只）。第 0 天经静脉内注射 60mg/kg 碘酸钠诱导视网膜变性。碘酸钠注射后第 4 天，干预组右眼同时接受静脉内和视网膜下 DPSCs 注射，载体组右眼接受视网膜下 Hank's 平衡盐溶液和静脉内生理盐水注射，阴性对照组右眼不做任何处理。在第 0 天（基线）、第 4 天、第 11 天、第 18 天、第 26 天和第 32 天进行视网膜电图（ERG）评估以评估视网膜功能。在第 32 天研究结束时，处死大鼠，取出其眼球进行组织学检查。
结果
实验组间最大 ERG a 波（p=0.107）和 b 波（p=0.153）振幅无显著差异。然而，3 组间研究眼明视 30Hz 闪烁振幅存在显著差异（p=0.032）。在干预组中，所有 6 只右眼（均接受视网膜下 DPSCs 注射）的 30Hz 闪烁 ERG 反应均有改善，而未经治疗的左眼 30Hz 闪烁 ERG 仍保持平坦。组织学显示干预组外核层厚度增加，但与阴性对照组和载体组相比，差异无统计学意义。
结论
视网膜下和静脉内注射 DPSCs 的联合应用可能有潜力从 NaIO 诱导的视网膜损伤模型中挽救视锥细胞功能。
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