John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
School of Pharmacy, University of East Anglia, Norwich, United Kingdom.
Stem Cells. 2018 Jan;36(1):65-78. doi: 10.1002/stem.2722. Epub 2017 Oct 31.
Optic neuropathies such as glaucoma occur when retinal ganglion cells (RGCs) in the eye are injured. Strong evidence suggests mesenchymal stem cells (MSCs) could be a potential therapy to protect RGCs; however, little is known regarding their effect on the human retina. We, therefore, investigated if human MSCs (hMSCs), or platelet-derived growth factor (PDGF) as produced by hMSC, could delay RGC death in a human retinal explant model of optic nerve injury. Our results showed hMSCs and the secreted growth factor PDGF-AB could substantially reduce human RGC loss and apoptosis following axotomy. The neuroprotective pathways AKT, ERK, and STAT3 were activated in the retina shortly after treatments with labeling seen in the RGC layer. A dose dependent protective effect of PDGF-AB was observed in human retinal explants but protection was not as substantial as that achieved by culturing hMSCs on the retina surface which resulted in RGC cell counts similar to those immediately post dissection. These results demonstrate that hMSCs and PDGF have strong neuroprotective action on human RGCs and may offer a translatable, therapeutic strategy to reduce degenerative visual loss. Stem Cells 2018;36:65-78.
当眼睛中的视网膜神经节细胞 (RGC) 受损时，就会发生视神经病变，如青光眼。有强有力的证据表明间充质干细胞 (MSCs) 可能是一种保护 RGC 的潜在治疗方法；然而，对于它们对人视网膜的影响知之甚少。因此，我们研究了人 MSCs (hMSCs) 或由 hMSC 产生的血小板衍生生长因子 (PDGF) 是否可以延迟视神经损伤的人视网膜外植体模型中 RGC 的死亡。我们的结果表明，hMSCs 和分泌的生长因子 PDGF-AB 可以在轴突切断后显著减少人 RGC 的损失和细胞凋亡。在治疗后不久，视网膜中就会出现 AKT、ERK 和 STAT3 神经保护途径的激活，在视网膜外植体中观察到 PDGF-AB 的剂量依赖性保护作用，但与 hMSC 在视网膜表面培养所达到的保护作用相比，这种作用并不显著，后者导致 RGC 细胞计数与解剖后立即相似。这些结果表明，hMSCs 和 PDGF 对人 RGC 具有很强的神经保护作用，可能提供一种可转化的治疗策略，以减少退行性视觉丧失。《干细胞》2018 年；36:65-78。
