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

Autor: Teixeira-Pinheiro LC; Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa, Brazil. Electronic address: leandrocoelho@biof.ufrj.br., Toledo MF; Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa, Brazil., Nascimento-Dos-Santos G; Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil., Mendez-Otero R; Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa, Brazil., Mesentier-Louro LA; Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil; Department of Ophthalmology, Stanford University, Palo Alto, USA., Santiago MF; Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, 21941-902, Brazil; Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa, Brazil.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2020 Nov; Vol. 200, pp. 108212. Date of Electronic Publication: 2020 Sep 08.
DOI: 10.1016/j.exer.2020.108212
Abstrakt: 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.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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