Abstract
Aims/Purpose: Sepsis causes systemic inflammation (SI) and induces acute and long‐term neurological dysfunctions. In the retina, SI causes the loss of retinal ganglion cells (RGCs). Advanced cell therapy with bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) is a promising avenue for RGCs neuroprotection in SI due to their immunomodulatory properties. Here we analyze the neuroprotective properties of BM‐MSCs in two transplantation settings: xenogeneic and allogeneic in a murine model of SI induced by lipopolysaccharide (LPS).Methods: 2‐month‐old C57BL/6J male mice were used in all groups. LPS was intraperitoneally injected (5mg/kg) at day 0. At day 1, BM‐MSCs isolated from BALB/C mice (allogenic) or human donors (xenogenic) were intravitreally administered in the left eye. As controls we used intact and LPS‐treated C57BL/6J animals. RGCs survival (Brn3a+) and microglial activation (Iba1+) were studied at 7 days in both retinas, the treated and the contralateral to the injection.Results: BM‐MSCs were found forming an epiretinal membrane in both transplant modalities. RGCs death in LPS controls reached 20% of the original population. The allogeneic transplant rescued all RGCs in both eyes. In contrast, xenogeneic transplant only protected to the contralateral eyes and microglia were more activated and reactive.Conclusions: These preclinical data show that allogeneic BM‐MSCs elicits a greater neuroprotection for sepsis induced RGCs degeneration in both eyes, the treated and contralateral. While the xenogeneic transplant does not neuroprotect RGCs in the treated eye, it does in the contralateral one, a neuroprotection that could be due to paracrine effects. These findings may be the basis to treat sepsis induced neurodegeneration.
Published Version
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