Paracrine signaling of human mesenchymal stem cell modulates retinal microglia population number and phenotype in vitro.

Abstract 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.