Purpose

Cellular therapy with mesenchymal stem cells (MSC) is emerging as an effective option to treat optic neuropathies. In models of retinal degeneration, MSC injected in the vitreous body protects injured retinal ganglion cells and stimulate their regeneration, however the mechanism is still unknown. Considering the immunomodulating proprieties of MSC and the controversial role of microglial contribution on retinal regeneration, we developed an in vitro co-culture model to analyze the effect of MSC on retinal microglia population.

Methods

We used whole adult rat retinal explants in co-culture with human Wharton's jelly mesenchymal stem cells (hMSC) separated by a transwell membrane and analyzed hMSC effect on both retinal ganglion cells (RGCs) and retinal microglia.

Results

hMSC in co-culture protected RGCs after 3 days in vitro by paracrine signaling. In addition, hMSC reduced microglia population and inhibited the pro-inflammatory phenotype of the remaining microglia.

Conclusions

Using a co-culture model, we demonstrated the paracrine effect of hMSC on RGC survival after injury concomitant with a reduction of microglial population. Paracrine signaling of hMSC also changed microglia phenotype and the expression of antiinflammatory factors in the retina. Our results are consistent with a detrimental effect of microglia on RGC survival and regeneration after injury.

中文翻译：

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人间充质干细胞的旁分泌信号传导在体外调节视网膜小胶质细胞数量和表型。

目的

间充质干细胞（MSC）的细胞疗法正在成为治疗视神经病变的有效选择。在视网膜变性模型中，注入玻璃体的MSC保护受损的视网膜神经节细胞并刺激其再生，但是其机制仍然未知。考虑到MSC的免疫调节特性以及小胶质细胞对视网膜再生的作用的争议，我们建立了体外共培养模型来分析MSC对视网膜小胶质细胞群体的影响。

方法

我们将完整的成年大鼠视网膜外植体与人沃顿氏胶质间充质干细胞（hMSC）通过透孔膜分开培养，并分析了hMSC对视网膜神经节细胞（RGCs）和视网膜小胶质细胞的作用。

结果

共培养物中的hMSC在体外3天后通过旁分泌信号传导保护了RGC 。此外，hMSC减少了小胶质细胞的数量，并抑制了其余小胶质细胞的促炎表型。

结论

使用共培养模型，我们证明了hMSC的旁分泌作用对损伤后伴有小胶质细胞减少的RGC存活的影响。hMSC的旁分泌信号传导也改变了小胶质细胞表型和视网膜中抗炎因子的表达。我们的结果与小胶质细胞对RGC损伤后存活和再生的有害作用相一致。