Neuroscience Research Lab, Department of Neurology, 29751Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Department of Biophysics, 29751Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Cell Transplant. 2020 Jan-Dec;29:963689720946031. doi: 10.1177/0963689720946031.
A number of degenerative conditions affecting the neural retina including age-related macular degeneration have no successful treatment, resulting in partial or complete vision loss. There are a number of stem cell replacement strategies for recovery of retinal damage using cells from variable sources. However, literature is still deficit in the comparison of efficacy of types of stem cells. The purpose of the study was to compare the therapeutic efficacy of undifferentiated cells, i.e., lineage negative stem cells (Lin-ve SC) with differentiated neurosphere derived from ciliary epithelium (CE) cells on retinal markers associated with laser-induced retinal injury. Laser-induced photocoagulation was carried out to disrupt Bruch's membrane and retinal pigmented epithelium in C57BL/6 mouse model. Lineage negative cells were isolated from human umbilical cord blood, whereas neurospheres were derived from CE of post-aborted human eyeballs. The cells were then transplanted into subretinal space to study their effect on injury. Markers of neurotropic factors, retina, apoptosis, and proliferation were analyzed after injury and transplantation. mRNA expression was also analyzed by real-time polymerase chain reaction at 1 week, and 3-month immunohistochemistry was evaluated at 1-week time point. CE cell transplantation showed enhanced differentiation of rods and retinal glial cells. However, Lin-ve cells exerted paracrine-dependent modulation of neurotrophic factors, which is possibly mediated by antiapoptotic and proliferative effects. In conclusion, CE transplantation showed superior regenerative outcome in comparison to Lin-ve SC for rescue of artificially injured rodent retinal cells. It is imperative that this source for transplantation may be extensively studied in various doses and additional retinal degeneration models for prospective clinical applications.
许多影响神经视网膜的退行性疾病,包括年龄相关性黄斑变性,目前尚无有效的治疗方法,导致部分或完全视力丧失。有许多基于干细胞的替代策略可以恢复视网膜损伤,使用的细胞来源于各种不同的来源。然而,关于不同类型的干细胞的疗效比较,文献仍然存在不足。本研究旨在比较未分化细胞,即谱系阴性干细胞(Lin-ve SC)与睫状上皮(CE)细胞来源的神经球在激光诱导的视网膜损伤相关视网膜标志物上的治疗效果。通过激光诱导光凝破坏 C57BL/6 小鼠模型中的布鲁赫膜和视网膜色素上皮。从人脐带血中分离出 Lin-ve 细胞,而神经球则来源于流产人眼球的 CE。然后将这些细胞移植到视网膜下腔,以研究它们对损伤的影响。在损伤和移植后分析神经营养因子、视网膜、细胞凋亡和增殖的标志物。通过实时聚合酶链反应在 1 周时分析 mRNA 表达,并在 1 周时进行 3 个月的免疫组织化学评估。CE 细胞移植显示杆状细胞和视网膜神经胶质细胞的分化增强。然而,Lin-ve 细胞发挥了旁分泌依赖性的神经营养因子调节作用,这可能是通过抗细胞凋亡和增殖作用介导的。总之,与 Lin-ve SC 相比,CE 移植在拯救人为损伤的啮齿动物视网膜细胞方面显示出更好的再生效果。必须对这种移植来源进行广泛研究,包括不同剂量和其他视网膜变性模型,以进行前瞻性临床应用。