Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury
Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury
复制标题
人牙周膜来源的干细胞促进视神经损伤后视网膜神经节细胞的存活和轴突再生。
DOI：
10.1002/stem.2812
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发表时间：
2018-06-01
期刊：
影响因子：
5.2
通讯作者：
Pang, Chi Pui
中科院分区：
文献类型：
--
作者：
Cen, Ling-Ping;Ng, Tsz Kin;Pang, Chi Pui
在发达国家，视神经病变是不可逆失明和视力损害的主要原因，全球受其影响的人数超过8000万。虽然大多数视神经病变没有有效的治疗方法，但对视网膜神经节细胞（RGC）保护和轴突再生的研究十分深入。我们先前已经证明了人牙周膜衍生干细胞（PDLSCs）用于视网膜细胞替代的潜力。在此，我们报道了人PDLSCs在视神经挤压（ONC）损伤后减轻RGC变性和促进轴突再生的神经保护作用。在体内ONC后，将人PDLSCs玻璃体内注射到成年Fischer大鼠的玻璃体腔中，并在体外与视网膜外植体共培养。人PDLSCs在玻璃体腔中存活，即使在ONC后3周仍维持在RGC层上。对Ⅲ型微管蛋白和生长相关蛋白43（Gap43）的免疫荧光分析表明，在人PDLSC移植的大鼠中，存活的RGCs数量和再生轴突数量显著增加。体外共培养实验证实，PDLSCs在不诱导炎症反应的情况下提高了视网膜外植体中RGC的存活率和神经突再生。直接的细胞 - 细胞相互作用以及脑源性神经营养因子分泌增加，而非促进内源性祖细胞再生，是人类PDLSCs保护RGC的机制。总之，我们的结果揭示了人PDLSCs通过在体内和体外强烈促进RGC存活和轴突再生而发挥的神经保护作用，表明其在针对视神经病变保护RGC方面具有治疗潜力。
Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury. Human PDLSCs were intravitreally injected into the vitreous chamber of adult Fischer rats after ONC in vivo as well as cocultured with retinal explants in vitro. Human PDLSCs survived in the vitreous chamber and were maintained on the RGC layer even at 3 weeks after ONC. Immunofluorescence analysis of III-tubulin and Gap43 showed that the numbers of surviving RGCs and regenerating axons were significantly increased in the rats with human PDLSC transplantation. In vitro coculture experiments confirmed that PDLSCs enhanced RGC survival and neurite regeneration in retinal explants without inducing inflammatory responses. Direct cell-cell interaction and elevated brain-derived neurotrophic factor secretion, but not promoting endogenous progenitor cell regeneration, were the RGC protective mechanisms of human PDLSCs. In summary, our results revealed the neuroprotective role of human PDLSCs by strongly promoting RGC survival and axonal regeneration both in vivo and in vitro, indicating a therapeutic potential for RGC protection against optic neuropathies.